Instrument detection and pose estimation with rigid part mixtures model in video-assisted surgeries

Publication date: Available online 30 March 2018
Source:Medical Image Analysis
Author(s): Daniel Wesierski, Anna Jezierska
Localizing instrument parts in video-assisted surgeries is an attractive and open computer vision problem. A working algorithm would immediately find applications in computer-aided interventions in the operating theater. Knowing the location of tool parts could help virtually augment visual faculty of surgeons, assess skills of novice surgeons, and increase autonomy of surgical robots. A surgical tool varies in appearance due to articulation, viewpoint changes, and noise. We introduce a new method for detection and pose estimation of multiple non-rigid and robotic tools in surgical videos. The method uses a rigidly structured, bipartite model of end-effector and shaft parts that consistently encode diverse, pose-specific appearance mixtures of the tool. This rigid part mixtures model then jointly explains the evolving tool structure by switching between mixture components. Rigidly capturing end-effector appearance allows explicit transfer of keypoint meta-data of the detected components for full 2D pose estimation. The detector can as well delineate precise skeleton of the end-effector by transferring additional keypoints. To this end, we propose effective procedure for learning such rigid mixtures from videos and for pooling the modeled shaft part that undergoes frequent truncation at the border of the imaged scene. Notably, extensive diagnostic experiments inform that feature regularization is a key to fine-tune the model in the presence of inherent appearance bias in videos. Experiments further illustrate that estimation of end-effector pose improves upon including the shaft part in the model. We then evaluate our approach on publicly available datasets of in-vivo sequences of non-rigid tools and demonstrate state-of-the-art results.

Graphical abstract

https://ift.tt/2GqoY5I

Deep Embedding Convolutional Neural Network for Synthesizing CT Image from T1-Weighted MR Image

Publication date: Available online 30 March 2018
Source:Medical Image Analysis
Author(s): Lei Xiang, Qian Wang, Dong Nie, Lichi Zhang, Xiyao Jin, Yu Qiao, Dinggang Shen
Recently, more and more attention is drawn to the field of medical image synthesis across modalities. Among them, the synthesis of computed tomography (CT) image from T1-weighted magnetic resonance (MR) image is of great importance, although the mapping between them is highly complex due to large gaps of appearances of the two modalities. In this work, we aim to tackle this MR-to-CT synthesis task by a novel deep embedding convolutional neural network (DECNN). Specifically, we generate the feature maps from MR images, and then transform these feature maps forward through convolutional layers in the network. We can further compute a tentative CT synthesis from the midway of the flow of feature maps, and then embed this tentative CT synthesis result back to the feature maps. This embedding operation results in better feature maps, which are further transformed forward in DECNN. After repeating this embedding procedure for several times in the network, we can eventually synthesize a final CT image in the end of the DECNN. We have validated our proposed method on both brain and prostate imaging datasets, by also comparing with the state-of-the-art methods. Experimental results suggest that our DECNN (with repeated embedding operations) demonstrates its superior performances, in terms of both the perceptive quality of the synthesized CT image and the run-time cost for synthesizing a CT image.



https://ift.tt/2pTq2Jf

Datasets for correlation dynamics of cocoa production in South Western Nigeria

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): S.O. Edeki, M.E. Adeosun, G.O. Akinlabi, O.M. Ofuyatan
In the Nigeria economy, cocoa production has been of great importance. This buttresses the fact that cocoa as a product is the leading agricultural export of Nigeria, leaving the country currently as the world fourth largest producer of cocoa, after Ivory Coast, Indonesia and Ghana and the third largest exporter, after Ivory Coast and Ghana. Hence, there is need for the agricultural sector expansion, effective predictive models and reliable price mechanism. This article examines tonnes of cocoa production dataset of the Nigeria agricultural sector for the period of twenty-four (24) years spanning between 1993 to 2016. The Correlation dynamics examined includes the autocorrelation features as affected by the production rate within the considered time interval. The degree of similarity between the dataset and the corresponding lagged version of itself over successive time interval is measured using a serial correlation test while the results mostly favour negative correlation showing that large current values correspond to small values at the specified lag. These dataset can effectively serve as good candidate for agricultural product modelling in terms of forecasting.



https://ift.tt/2E7fLxh

Taiwanese consumer survey data for investigating the role of information on equivalence of organic standards in directing food choice

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Ching-Hua Yeh, Monika Hartmann, Stefan Hirsch
The presentation of credence attributes such as the product's origin or the production method has a significant influence on consumers' food purchase decisions. The dataset includes survey responses from a discrete choice experiment with 1309 food shoppers in Taiwan using the example of sweet pepper. The survey was carried out in 2014 in the three largest Taiwanese cities. It evaluates the impact of providing information on the equality of organic standards on consumers' preferences at the example of sweet pepper. Equality of organic standards implies that regardless of products' country-of-origin (COO) organic certifications are based on the same production regulation and managerial processes. Respondents were randomly allocated to the information treatment and the control group. The dataset contains the product choices of participants in both groups, as well as their sociodemographic information.



https://ift.tt/2pU4bAr

Data on drying kinetics of a semi-automated gas-fired fish dryer

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Idehai O. Ohijeagbon, Olumuyiwa A. Lasode, Segun Adebayo, Oluseyi O. Ajayi, Olugbenga A. Omotosho
The dataset presented in this article represent the drying characteristics of a semi-automated gas-fired fish dryer. A cabinet dryer was constructed mainly from mild steel sheet metal and stainless steel, and was used for drying prepared fish samples of Clarias gariepinus species. Major operating parameters which included mass of fish, mass of Liquefied Petroleum Gas used, inside temperature of the dryer, and drying time were monitored. Also, output parameters such as the moisture content and energy utilization amongst others were observed and recorded at varying time intervals and specified drying temperatures. The drying temperature was sustained via an incorporated PID temperature controller that allowed drying to proceed until a relatively constant mass of the dried fish samples was attained. The information contained in this data article include a schematic drawing of drying kinetics analysis of the semi-automated gas-fired fish dryer and a pictorial view of the gas-fired cabinet dryer. Also included are pictorial representations of the washed and neatly folded degutted fish samples and dried fish samples. Data provided in this article are those relating to process parameters of the semi-automated fish dryer, data of output parameters of the fish dryer and comparisons of moisture content and energy utilization at different drying temperatures with time.



https://ift.tt/2J5sB2R

Hourly pattern of allergenic alder and birch pollen concentrations in the air: Spatial differentiation and the effect of meteorological conditions

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): K. Borycka, I. Kasprzyk
In temperate climate widespread alder and birch are an important source of strong aeroallergens. The diurnal pattern of airborne pollen concentrations depends on the rhythm of pollen release from anthers as well as weather conditions, convection air currents, long-distance transport, pollen trap location and local vegetation. The aim of the study was to present a diurnal pattern of Alnus (alder) and Betula (birch) pollen concentrations in the air in a horizontal and vertical gradient and examine the weather parameters that had the greatest impact on the pattern. The study was conducted in Rzeszów City, southeast Poland over three years. Pollen grains were collected using a Hirst volumetric spore trap at three sampling points: two at 12 m the agl, and one at 1.5 m agl. Data were analysed using circular statistics and a nonlinear function. For alder, three models of hourly patterns were elaborated and the most common presented early morning minimum and early afternoon maximum. For birch, the most common model has one peak at night and a marked decrease in concentrations in early morning, although a second model has peak during early afternoon. A model with 3 peaks is much less common. These models are characteristic for warm temperate climate regions, where alders and birches are common. The diurnal patterns did not depend on the localization of traps or proximity of the pollen source, although these factors influenced the hourly concentrations, with higher values observed at roof level. Significant relationships between the hourly pollen counts and meteorological parameters were observed only for alder. Three incidents of increasing birch pollen concentrations were observed during the first two hours of precipitation and linked to a convection effect. Unstable weather conditions caused by air convection might strongly modify the circadian pattern and cause the nightly peaks concentrations. The general results are that people suffering from allergies may be exposed to high birch and alder pollen concentrations at almost all times during the day with the exception of the morning hours, as well as during the first hours of convective precipitation. Precise information on pollen concentrations aids in allergy prevention, so cities should provide aerobiological monitoring at least at "roof level" and "nose level".

Graphical abstract

https://ift.tt/2GY1N3L

Air quality and human health impacts of grasslands and shrublands in the United States

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Varsha Gopalakrishnan, Satoshi Hirabayashi, Guy Ziv, Bhavik R. Bakshi
Vegetation including canopy, grasslands, and shrublands can directly sequester pollutants onto the plant surface, resulting in an improvement in air quality. Until now, several studies have estimated the pollution removal capacity of canopy cover at the level of a county, but no such work exists for grasslands and shrublands. This work quantifies the air pollution removal capacity of grasslands and shrublands at the county-level in the United States and estimates the human health benefits associated with pollution removal using the i-Tree Eco model. Sequestration of pollutants is estimated based on the Leaf Area Index (LAI) obtained from the Moderate Resolution Imaging Spectroradiometer (MODIS) derived dataset estimates of LAI and the percentage land cover obtained from the National Land Cover Database (NLCD) for the year 2010. Calculation of pollution removal capacity using local environmental data indicates that grasslands and shrublands remove a total of 6.42 million tonnes of air pollutants in the United States and the associated monetary benefits total $268 million. Human health impacts and associated monetary value due to pollution removal was observed to be significantly high in urban areas indicating that grasslands and shrublands are equally critical as canopy in improving air quality and human health in urban regions.

Graphical abstract

https://ift.tt/2pUuaYz

Experimental investigation of tread wear and particle emission from tyres with different treadwear marking

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Theodoros Grigoratos, Mats Gustafsson, Olle Eriksson, Giorgio Martini
The Treadwear Rating (TWR) provided on the sidewall of the tyre is a marking intended to inform the customer about the expected durability of the tyre. The current study explores whether there is a correlation between the TWR and tyres' tread mass loss. Furthermore, it explores the possible correlation between the TWR and tyre wear dust emitted in the form of PM10 and PM2.5. For that reason, two tyres of the same brand (B) but with different TWR and three tyres of different brands (C and D with the same TWR as one of the B tyres and A with a lower TWR) were tested at a constant speed of 70 km/h by means of the Swedish National Road and Transport Research Institute (VTI) road simulator. Tyres of the same TWR but of different brands showed different behaviour in terms of material loss, PM, and PN emissions under the selected testing conditions. This means that it is not feasible to categorize tyres of different brands in terms of their emissions based on their TWR. The test performed on the two tyres of the same brand but with different TWR showed instead a substantial (not statistically significant) difference in both total wear and PM10 emissions. The tyre with the higher TWR (B2) showed less wear and PM10 emissions compared to the B1 tyre having a lower TWR. Since only two tyres of the same brand and with different TWR were tested, this result cannot be generalized and more tests are necessary to confirm the relation within the same brand. In general, the tyre tread mass loss showed no obvious statistical relation to PM10, PM2.5 or PN concentration. In all cases approximately 50% (by mass) of emitted PM10 fall within the size range of fine particles, while PN size distribution is dominated by nanoparticles most often peaking at 20–30 nm.



https://ift.tt/2GX7RcE

Operational evaluation of the RLINE dispersion model for studies of traffic-related air pollutants

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Chad W. Milando, Stuart A. Batterman
Exposure to traffic-related air pollutants (TRAP) remains a key public health issue, and improved exposure measures are needed to support health impact and epidemiologic studies and inform regulatory responses. The recently developed Research LINE source model (RLINE), a Gaussian line source dispersion model, has been used in several epidemiologic studies of TRAP exposure, but evaluations of RLINE's performance in such applications have been limited. This study provides an operational evaluation of RLINE in which predictions of NOx, CO and PM2.5 are compared to observations at air quality monitoring stations located near high traffic roads in Detroit, MI. For CO and NOx, model performance was best at sites close to major roads, during downwind conditions, during weekdays, and during certain seasons. For PM2.5, the ability to discern local and particularly the traffic-related portion was limited, a result of high background levels, the sparseness of the monitoring network, and large uncertainties for certain processes (e.g., formation of secondary aerosols) and non-mobile sources (e.g., area, fugitive). Overall, RLINE's performance in near-road environments suggests its usefulness for estimating spatially- and temporally-resolved exposures. The study highlights considerations relevant to health impact and epidemiologic applications, including the importance of selecting appropriate pollutants, using appropriate monitoring approaches, considering prevailing wind directions during study design, and accounting for uncertainty.



https://ift.tt/2E8UoeO

Temporal and spatial characteristics of dust devils and their contribution to the aerosol budget in East Asia—An analysis using a new parameterization scheme for dust devils

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Yaoguo Tang, Yongxiang Han, Zhaohuan Liu
Dust aerosols are the main aerosol components of the atmosphere that affect climate change, but the contribution of dust devils to the atmospheric dust aerosol budget is uncertain. In this study, a new parameterization scheme for dust devils was established and coupled with WRF-Chem, and the diurnal and monthly variations and the contribution of dust devils to the atmospheric dust aerosol budget in East Asia was simulated. The results show that 1) both the diurnal and monthly variations in dust devil emissions in East Asia had unimodal distributions, with peaks in the afternoon and the summer that were similar to the observations; 2) the simulated dust devils occurred frequently in deserts, including the Gobi. The distributed area and the intensity center of the dust devil moved from east to west during the day; 3) the ratio between the availability of convective buoyancy relative to the frictional dissipation was the main factor that limited the presence of dust devils. The position of the dust devil formation, the surface temperature, and the boundary layer height determined the dust devil intensity; 4) the contribution of dust devils to atmospheric dust aerosols determined in East Asia was 30.4 ± 13%, thereby suggesting that dust devils contribute significantly to the total amount of atmospheric dust aerosols. Although the new parameterization scheme for dust devils was rough, it was helpful for understanding the distribution of dust devils and their contribution to the dust aerosol budget.

Graphical abstract

https://ift.tt/2GX7LBO

VOCs emission characteristics and priority control analysis based on VOCs emission inventories and ozone formation potentials in Zhoushan

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Qiaoli Wang, Sujing Li, Minli Dong, Wei Li, Xiang Gao, Rongmin Ye, Dongxiao Zhang
Zhoushan is an island city with booming tourism and service industry, but also has many developed VOCs and/or NOX emission industries. It is necessary to carry out regional VOCs and O3 pollution control in Zhoushan as the only new area owns the provincial economic and social administration rights. Anthropogenic VOCs emission inventories were built based on emission factor method and main emission sources were identified according to the emission inventories. Then, localized VOCs source profiles were built based on in-site sampling and referring to other studies. Furthermore, ozone formation potentials (OFPs) profiles were built through VOCs source profiles and maximum incremental reactivity (MIR) theory. At last, the priority control analysis results showed that industrial processes, especially surface coating, are the key of VOCs and O3 control. Alkanes were the most emitted group, accounting for 58.67%, while aromatics contributed the most to ozone production accounting for 69.97% in total OFPs. n-butane, m/p-xylene, i-pentane, n-decane, toluene, propane, n-undecane, o-xylene, methyl cyclohexane and ethyl benzene were the top 10 VOC species that should be preferentially controlled for VOCs emission control. However, m/p-xylene, o-xylene, ethylene, n-butane, toluene, propene, 1,2,4-trimethyl benzene, 1,3,5-trimethyl benzene, ethyl benzene and 1,2,3-trimethyl benzene were the top 10 VOC species that required preferential control for O3 pollution control.



https://ift.tt/2E87oBE

A new methodology to derive settleable particulate matter guidelines to assist policy-makers on reducing public nuisance

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Milena Machado, Jane Meri Santos, Valdério Anselmo Reisen, Neyval Costa Reis, Ilias Mavroidis, Ana T. Lima
Air quality standards for settleable particulate matter (SPM) are found in many countries around the world. As well known, annoyance caused by SPM can be considered a community problem even if only a small proportion of the population is bothered at rather infrequent occasions. Many authors have shown that SPM cause soiling in residential and urban environments and degradation of materials (eg, objects and surface painting) that can impair the use and enjoyment of property and alter the normal activities of society. In this context, this paper has as main contribution to propose a guidance to establish air quality standards for annoyance caused by SPM in metropolitan industrial areas. To attain this objective, a new methodology is proposed which is based on the nonlinear correlation between the perceived annoyance (qualitative variable) and particles deposition rate (quantitative variable). Since the response variable is binary (annoyed and not annoyed), the logistic regression model is used to estimate the probability of people being annoyed at different levels of particles deposition rate and to compute the odds ratio function which gives, under a specific level of particles deposition rate, the estimated expected value of the population perceived annoyance. The proposed methodology is verified in a data set measured in the metropolitan area of Great Vitória, Espirito Santo, Brazil. As a general conclusion, the estimated probability function of perceived annoyance as a function of SPM has shown that 17% of inhabitants report annoyance to very low particles deposition levels of 5 g/(m²∙30 days). In addition, for an increasing of 1 g/(m²∙30 days) of SPM, the smallest estimated odds ratio of perceived annoyance by a factor of 1.5, implying that the probability of occurrence is almost 2 times as large as the probability of no occurrence of annoyance.

Graphical abstract

https://ift.tt/2H0ReNy

Diurnal spatial distributions of aerosol optical and cloud micro-macrophysics properties in Africa based on MODIS observations

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Didier Ntwali, Hongbin Chen
The diurnal spatial distribution of both natural and anthropogenic aerosols, as well as liquid and ice cloud micro-macrophysics have been evaluated over Africa using Terra and Aqua MODIS collection 6 products. The variability of aerosol optical depth (AOD), Ångström exponent (AE), liquid and ice cloud microphysics (Liquid cloud effective radius LCER, Ice cloud effective radius ICER) and cloud macrophysics (Liquid cloud optical thickness LCOT, Liquid cloud water path LCWP, Ice cloud optical thickness ICOT, Ice cloud water path ICWP) parameters were investigated from the morning to afternoon over Africa from 2010 to 2014. In both the morning (Terra) and afternoon (Aqua) heavy pollution (AOD ≥ 0.6) occurs in the coastal and central areas (between 12⁰ N-17⁰ N and 10⁰ E-15⁰ E) of West of Africa (WA), Central of Africa (CA) (0.5⁰ S-7⁰S and 10⁰ E-25⁰ E),. Moderate pollution (0.3 < AOD < 0.6) often occurs in West and North of Africa (between 5⁰ N-27⁰ N and 16⁰ W-5⁰E), and clean environmental (AOD < 0.3) conditions are common in South of Africa (SA), East of Africa (EA) and some regions in North of Africa (NA). The West-North of Africa (WNA) and Central-South of Africa (CSA) regions are dominated by dust (AE < 0.7) and biomass burning (AE > 1.2) aerosols. The mixture of dust and biomass burning aerosols (0.7 < AE < 1.2) are found at the coastal areas in West of Africa (CoWA) and Central of Africa (CA) (5⁰ N-8⁰N and 10⁰ E-34⁰ E), particularly in the morning and afternoon respectively. The LCER often decrease from the morning to the afternoon in all seasons, but an increase occur from the morning to the afternoon in CSA (5⁰ S-22⁰ S) in DJF, both CA (2⁰ S-5⁰N) and CoWA in JJA and SON. The ICER increase from the morning to afternoon in all seasons over Africa and decreases in South of Africa (5⁰ S-20⁰ S) in DJF. The LCOT increases from the morning to afternoon in NA and SA while a decrease occur in CA in all seasons. The LCWP increase in many regions of Africa in all seasons while a decrease occurs in CoWA during JJA. The ICOT and ICWP show a remarkable increase from the morning to afternoon in regions dominated by biomass burning (CSA) compared to regions dominated by dust (WNA) aerosols in DJF, MAM and SON. Dust aerosols are mainly distributed in WNA by northerly and westerly winds in both January and April, southerly and southwesterly winds in July, and southerly and southwesterly winds in October, while biomass burning aerosols are mainly distributed in CSA by the northerly and northeasterly winds in January, easterly winds in April, July and October. The diurnal variability of cloud parameters is associated with both convective processes and cloud types. The knowledge of interactions between natural and anthropogenic aerosols with liquid and ice cloud microphysics parameters could contribute to improve aerosol and cloud remote sensing retrieval.



https://ift.tt/2E795PJ

A fast sample processing strategy for large-scale profiling of human urine phosphoproteome by mass spectrometry

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Xinyuan Zhao, Wanjun Zhang, Tong Liu, Hangyan Dong, Junjie Huang, Changqing Sun, Guangshun Wang, Xiaohong Qian, Weijie Qin
Liquid biopsies using body fluids have gained much attention in recent years due to their multiple advantages in clinical diagnosis, such as less/non-invasive collection, suitability for longitudinal disease monitoring, and better representation of tumor heterogeneity. As an attractive choice for liquid biopsy, urine proteins and their post-translational modifications (PTMs) have the potential to offer significant insights into physiological variations and pathological changes in the human body. However, due to the intrinsically large variability of urine proteins and their PTMs among different individuals, there is a high demand for strategies for high-throughput analysis of a large number of samples to obtain a comprehensive view and a reliable reference interval of the urine proteome. In this work, we proposed a new urine phosphoproteome sample processing strategy that combines fast protein extraction, efficient multiple immobilized-proteases digestion, and tandemly connected centrifugal tips device-based facile phosphopeptide enrichment & fractionation. This strategy is capable of paralleled sample processing with an approximate five-fold reduction in processing time and is therefore particularly suitable for handling a large number of urine samples. Totally, we identified 4196 phosphosites in human urine proteins by mass spectrometry in replicated tests, a number which is dozens of times larger than those previously reported. Therefore, this strategy may have great potential in urine-based phosphoprotein biomarker screening and drug response studies.

Graphical abstract

https://ift.tt/2GYkHrc

Affinity capture surface carboxyl-functionalized MoS2 sheets to enhance the sensitivity of surface plasmon resonance immunosensors

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Nan-Fu Chiu, Ting-Li Lin
The development of functionalized molybdenum disulfide (MoS2) has led to a new trend in the biosensing field, owing to its high sensitivity and bio-affinity characteristics with regards to the simple synthesis of carboxyl-functionalized MoS2 nanocomposites. In this study, we used monochloroacetic acid (MCA) to successfully modify carboxyl-MoS2. The efficiency of this MCA modification method showed a higher -COOH group content of 30.1%, mainly due to chlorine atoms occupying the MoS2 sulfur vacancy to allow for the formation of a strong bonding effect. This then enhanced the surface area of -COOH and improved the formation of covalent bonds between proteins. We demonstrated that MoS2-COOH-based surface plasmon resonance (SPR) chips can provide excellent sensitivity and high affinity for immunoassay biomolecules detected in a low sample volume of 20 μl. With respect to the shifts of the SPR angles of the chips, the high binding affinity at a BSA concentration of 14.5 nM for a MoS2-COOH chip, a MoS2 chip and a traditional SPR chip are 4.69 m°, 2.49 m° and 1.53 m°, respectively. In addition, the MoS2-COOH chip could amplify the SPR angle response by 3.1 folds and enhance the high association rate of ka by 212 folds compared to MoS2 and traditional SPR chips. The results thus obtained revealed that the overall affinity binding value, KA, of the MoS2-COOH chip can be significantly enhanced by up to ∼ 6.5 folds that of the MoS2 chip. In summary, the excellent binding affinity, biocompatible and high sensitivity suggest the potential of the clinical application of this MoS2-COOH-based SPR chip detection method for in vitro diagnostic and point-of-care testing devices.

Graphical abstract

https://ift.tt/2pTLe0E

Synthesis of penetrable poly(methacrylic acid-co-ethylene glycol dimethacrylate) microsphere and its HPLC application in protein separation

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Xiao Sun, Jing Li, Li Xu
In the present study, the narrow-dispersed penetrable poly(methacrylic acid-co-ethylene glycol dimethacrylate) (poly(MAA-co-EDMA)) microspheres were successfully synthesized based on the sacrificial support method. The poly(MAA-co-EDMA) microspheres mirrored the porous structure of the sacrificial support, i.e. penetrable silica, characteristic of copious mesopores and throughpores. In addition, they possessed large surface area, adjustable hydrophobicity and the cation-exchange ability. Owing to their multi functionalities, they were applied as chromatographic stationary phase to separate proteins in different separation modes, including reversed phase, hydrophobic interaction and weak cation exchange. Moreover, thanks to their throughpores, fast separation at low column backpressure could be achieved in these three modes. Both protein recovery and column stability were satisfactory. The penetrable poly(MAA-co-EDMA) microspheres were potential stationary phase matrix for fast protein separation.

Graphical abstract

https://ift.tt/2GZUKYu

An update on the role of irisin in the regulation of endocrine and metabolic functions

Publication date: Available online 30 March 2018
Source:Peptides
Author(s): Mohamed Omer Mahgoub, Crystal D'Souza, Reem S.M.H. AlDarmaki, May M.Y.H. Baniyas, Ernest Adeghate
Irisin is a novel myokine and adipokine that has gained much attention recently due to its mechanisms of action. Irisin is secreted following proteolytic cleavage of its precursor fibronectin type III domain containing 5 (FNDC5). Following its release, irisin exerts its major action by increasing the expression of mitochondrial uncoupling protein 1 (UCP 1), which facilitates the conversion of white adipose tissue (WAT) into beige adipose tissue. Irisin is distributed in various body tissues and several actions have been attributed to its presence in those tissues. It has been suggested that it plays a role in metabolic diseases, ageing, inflammation and neurogenesis. However, the circulating levels of irisin are modulated by several factors such as diet, obesity, exercise, pharmacological agents and different pathological conditions. In this review, we have discussed the mechanisms by which irisin influences the functions of different body systems and how external factors in turn affect the circulating level of irisin. In conclusion, modification of circulating irisin level may help in the management of a variety of endocrine and metabolic disorders.

Graphical abstract

https://ift.tt/2uAYXPC

Editorial Board

Publication date: April 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1861, Issue 4





https://ift.tt/2GX63At

Multiple roles of lymphatic vessels in tumor progression

Publication date: August 2018
Source:Current Opinion in Immunology, Volume 53
Author(s): Qiaoli Ma, Lothar C Dieterich, Michael Detmar
Sentinel lymph node metastasis is a prognostic indicator for systemic tumor spread in many types of cancers, and tumor lymphangiogenesis correlates with reduced survival. Consequently, lymphatic vessels have been suggested to promote tumor progression in multiple ways. Tumor lymphangiogenesis occurs both in primary tumors and at distant (pre-) metastatic sites, and facilitates lymphatic invasion and tumor cell dissemination. Lymphatic vessels have also emerged as regulators of tumor immunity, transporting tumor antigens to lymph nodes and directly interacting with immune cells. Furthermore, lymphatic vessels might provide a 'lymphovascular' niche contributing to the maintenance of stem-like tumor cells that are tightly related to tumor recurrence. Thus, targeting tumor lymphangiogenesis or specific lymphatic-associated functions might represent a promising approach to inhibit tumor progression.



https://ift.tt/2J5SI9E

Next generation natural killer cells for cancer immunotherapy: the promise of genetic engineering

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): May Daher, Katayoun Rezvani
Recent advances in the field of cellular therapy have focused on autologous T cells engineered to express a chimeric antigen receptor (CAR) against tumor antigens. Remarkable responses have been observed in patients receiving autologous CD19-redirected T cells for the treatment of B-lymphoid malignancies. However, the generation of autologous products for each patient is logistically challenging and expensive. Extensive research efforts are ongoing to generate an off-the-shelf cellular product for the treatment of cancer patients. Natural killer (NK) cells are attractive contenders since they have potent anti-tumor activity, and their safety in the allogeneic setting expands the cell sources for NK cell therapy beyond an autologous one. In this review, we discuss advantages and limitations of NK cellular therapy, and novel genetic engineering strategies that may be applied to overcome some of the limitations. Next-generation engineered NK cells are showing great promise in the preclinical setting and it is likely that in the next few years CAR-engineered NK cells will be incorporated into the current armamentarium of cell-based cancer therapeutics.



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Editorial Board

Publication date: 15 April 2018
Source:Journal of Neuroscience Methods, Volume 300





https://ift.tt/2uA36n4

Preface: Special issue on measuring behaviour 2016

Publication date: 15 April 2018
Source:Journal of Neuroscience Methods, Volume 300
Author(s): Gernot Riedel, Cathal Gurrin, Andrew Spink




https://ift.tt/2pT0nAp

Lacking quality in research: Is behavioral neuroscience affected more than other areas of biomedical science?

Publication date: 15 April 2018
Source:Journal of Neuroscience Methods, Volume 300
Author(s): Anton Bespalov, Thomas Steckler
There are many reasons why novel therapeutics fail in clinical trials but these failures are often attributed to lacking quality of preclinical data. These problems are not limited to any specific therapeutic area, academic or industrial research and are due in large part to several generic factors influencing research quality (e.g., related to definition of pre-specified endpoints, principles of study design and analysis, biased reporting, and lack of proper training). Yet, neuroscience drug discovery is often said to be affected more than the other fields. Within neuroscience, behavioral studies are the most blamed for being poorly designed, underpowered and mis-reported and there are indeed several factors that may be rather unique for behavioral research, such as a multitude of environmental conditions that are difficult to control and that are often not reported, ethical concerns about in vivo research and the pressure to reduce animal numbers, contributing to under-powered studies, and the complexity of study design and analysis, creating too much room for post hoc data massaging and selective reporting. Also, the blood-brain barrier as a frequently neglected complicating factor has to be considered in CNS research. The importance of these factors is increasingly recognized and urgent efforts are needed to demonstrate that behavioral methods of preclinical neuroscience research deliver results that can be as robust as with the non-behavioral methods Until this goal is achieved, behavioral neuroscience and neuroscience in general may be losing young talent, CNS drug discovery may lack the needed investment and this field may indeed be amongst the most affected by the current preclinical data quality crisis.



https://ift.tt/2uHeYUr

Between and within laboratory reliability of mouse behaviour recorded in home-cage and open-field

Publication date: 15 April 2018
Source:Journal of Neuroscience Methods, Volume 300
Author(s): Lianne Robinson, Berry Spruijt, Gernot Riedel
BackgroundReproducibility of behavioural findings between laboratories is difficult due to behaviour being sensitive to environmental factors and interactions with genetics. The objective of this study was to investigate reproducibility of behavioural data between laboratories using the PhenoTyper home cage observation system and within laboratory reproducibility using different lighting regimes.New methodThe ambulatory activity of C57BL/6 and DBA/2 mice was tested in PhenoTypers in two laboratories under near identical housing and testing conditions (Exp. 1). Additionally activity and anxiety were also assessed in the open-field test. Furthermore, testing in either a normal or inverted light/dark cycle was used to determine effects of lighting regime in a within-laboratory comparison in Aberdeen (Exp. 2).ResultsUsing the PhenoTyper similar circadian rhythms were observed across laboratories. Higher levels of baseline and novelty-induced activity were evident in Aberdeen compared to Utrecht although strain differences were consistent between laboratories. Open field activity was also similar across laboratories whereas strain differences in anxiety were different. Within laboratory analysis of different lighting regimes revealed that behaviour of the mice was sensitive to changes in lighting.Comparison with existing methodsUtilisation of a home cage observation system facilitates the reproducibility of activity but not anxiety-related behaviours across laboratories by eliminating environmental factors known to influence reproducibility in standard behavioural tests.ConclusionsStandardisation of housing/test conditions resulted in reproducibility of home cage and open field activity but not anxiety-related phenotypes across laboratories with some behaviours more sensitive to environmental factors. Environmental factors include lighting and time of day.



https://ift.tt/2pRXDD7

High tech cognitive and acoustic enrichment for captive elephants

Publication date: 15 April 2018
Source:Journal of Neuroscience Methods, Volume 300
Author(s): Fiona French, Clara Mancini, Helen Sharp
This paper investigates the potential for using technology to support the development of sensory and cognitive enrichment activities for captive elephants. It explores the usefulness of applying conceptual frameworks from interaction design and game design to the problem of developing species-specific smart toys that promote natural behaviours and provide stimulation. We adopted a Research through Design approach, and describe how scientific inquiry supported our design process, while the creation of artefacts guided our investigations into possible future solutions. Our fieldwork resulted in the development of an interactive prototype of an acoustic toy that elephants are able to control using interface elements constructed from a range of natural materials.



https://ift.tt/2IhBs04

Extended, continuous measures of functional status in community dwelling persons with Alzheimer’s and related dementia: Infrastructure, performance, tradeoffs, preliminary data, and promise

Publication date: 15 April 2018
Source:Journal of Neuroscience Methods, Volume 300
Author(s): Bradley Zylstra, George Netscher, Julien Jacquemot, Michael Schaffer, Galen Shen, Angela D. Bowhay, Tamara L. Braley, Katherine L. Possin, Bruce L. Miller, Alexandre M. Bayen, Stephen J. Bonasera, A. Katrin Schenk
BackgroundThe past decades have seen phenomenal growth in the availability of inexpensive and powerful personal computing devices. Efforts to leverage these devices to improve health care outcomes promise to remake many aspects of healthcare delivery, but remain in their infancy.New methodWe describe the development of a mobile health platform designed for daily measures of functional status in ambulatory, community dwelling subjects, including those who have Alzheimer's disease or related neurodegenerative disorders. Using Smartwatches and Smartphones we measure subject overall activity and outdoor location (to derive their lifespace). These clinically-relevant measures allow us to track a subject's functional status in their natural environment over prolonged periods of time without repeated visits to healthcare providers. Functional status metrics are integrated with medical information and caregiver reports, which are used by a caregiving team to guide referrals for physician/APRN/NP care.Comparisonwith Existing Methods We describe the design tradeoffs involved in all aspects of our current system architecture, focusing on decisions with significant impact on system cost, performance, scalability, and user-adherence.ResultsWe provide real-world data from current subject enrollees demonstrating system accuracy and reliability.ConclusionsWe document real-world feasibility in a group of men and women with dementia that Smartwatches/Smartphones can provide long-term, relevant clinical data regarding individual functional status. We describe the underlying considerations of this system so that interested organizations can adapt and scale our approach to their needs. Finally, we provide a potential agenda to guide development of future systems.



https://ift.tt/2pOSZGc

The influence of hypoxia and IFN-γ on the proteome and metabolome of therapeutic mesenchymal stem cells

Publication date: June 2018
Source:Biomaterials, Volume 167
Author(s): Holly M. Wobma, Manuel A. Tamargo, Shahar Goeta, Lewis M. Brown, Raimon Duran-Struuck, Gordana Vunjak-Novakovic
Over the past 15 years, mesenchymal stem cells (MSCs) have been assessed for their capacity to suppress inflammation and promote tissue repair. Regardless of whether the cells are primed (exposed to instructive cues) before administration, their phenotype will respond to environmental signals present in the pathophysiological setting being treated. Since hypoxia and inflammation coexist in the settings of acute injury and chronic disease we sought to explore how the proteome and metabolome of MSCs changes when cells were exposed to 48 h of 1% oxygen, interferon gamma (IFN-γ), or both cues together. We specifically focused on changes in cell metabolism, immune modulation, extracellular matrix secretion and modification, and survival capacity. IFN-γ promoted expression of anti-pathogenic proteins and induced MSCs to limit inflammation and fibrosis while promoting their own survival. Hypoxia instead led to cell adaptation to low oxygen, including upregulation of proteins involved in anaerobic metabolism, autophagy, angiogenesis, and cell migration. While dual priming resulted in additive effects, we also found many instances of synergy. These data lend insight to how MSCs may behave after administration to a patient and suggest how priming cells beforehand could improve their therapeutic capacity.



https://ift.tt/2pS9oJU

Near infrared-emitting persistent luminescent nanoparticles for Hepatocellular Carcinoma imaging and luminescence-guided surgery

Publication date: June 2018
Source:Biomaterials, Volume 167
Author(s): Ting Ai, Wenting Shang, Hao Yan, Chaoting Zeng, Kun Wang, Yuan Gao, Tianpei Guan, Chihua Fang, Jie Tian
Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, is increasing nowadays and poses a serious threat to human health. However, if treated effectively and timely, it is clinically manageable or curable. Therefore, accurate detection and complete surgical resection remain priorities for HCC with a high potential of improving both survival and quality of life. Lacking of real-time guide technology, traditional surgery are usually relied on the subjective experience of surgeon, which have the limitation of high sensitivity detection tumor. Here, we developed a contrast agent, ZnGa2O4Cr0.004 (ZGC), used for guided surgery during operation to accurate delineation of HCC. ZGC showed excellent long-lasting afterglow properties that lasted for hours, which can aid in real-time guided surgery. Meanwhile, ZGC display high spatial resolution and deep penetration during pre-operation for diagnostic computed tomography (CT). Interestingly, we observed reverse imaging in the tumor region, known as a "dark hole", which further improves the contrast for surgery. This new multi-modality nanoparticle has great potential for accurate liver cancer imaging and resection guidance.

Graphical abstract

https://ift.tt/2uzhLPd

Nucleosome-inspired nanocarrier obtains encapsulation efficiency enhancement and side effects reduction in chemotherapy by using fullerenol assembled with doxorubicin

Publication date: June 2018
Source:Biomaterials, Volume 167
Author(s): Jinglong Tang, Ruirui Zhang, Mengyu Guo, Leihou Shao, Ying Liu, Yuliang Zhao, Suojiang Zhang, Yan Wu, Chunying Chen
Chemodrugs have been widely used to treat cancer; however, the chemotherapy usually leads to serious side effects and failure. Various nanomaterials and strategies have been explored for drug delivery to improve the efficacy of chemodrugs. One key to loading chemodrugs onto a nano-delivery system is enhancement of the encapsulation efficiency, especially for polymeric nanoparticles being loaded with hydrophilic drugs. Inspired by the ability of eukaryote to package millions of genes in the nucleus wrapping and condensing DNA around histones to form chromosomes, here we developed a karyon-like hybrid nanoparticle to achieve ultra-high encapsulation of doxorubicin (Dox) with reduced side effects. We utilized fullerenol as a "histone", packaged a great number of Dox, and used PEG-PLGA as the "karyotheca" coating the "nucleosome" (fullerenol and Dox complex) to stabilize the complex. It is noteworthy that the encapsulation efficiency of Dox in the polymeric micelles was increased from ∼5% to ∼79%. What's more, the biomimetic-inspired delivery system significantly reduced the chemodrug side effects by utilizing the radical scavenging ability of fullerenol. This novel drug-delivery design approach provides useful insights for improving the applicability of fullerenol in drug delivery systems for cancer therapy.

Graphical abstract

https://ift.tt/2pRTajM

The influence of hypoxia and IFN-γ on the proteome and metabolome of therapeutic mesenchymal stem cells

Publication date: June 2018
Source:Biomaterials, Volume 167
Author(s): Holly M. Wobma, Manuel A. Tamargo, Shahar Goeta, Lewis M. Brown, Raimon Duran-Struuck, Gordana Vunjak-Novakovic
Over the past 15 years, mesenchymal stem cells (MSCs) have been assessed for their capacity to suppress inflammation and promote tissue repair. Regardless of whether the cells are primed (exposed to instructive cues) before administration, their phenotype will respond to environmental signals present in the pathophysiological setting being treated. Since hypoxia and inflammation coexist in the settings of acute injury and chronic disease we sought to explore how the proteome and metabolome of MSCs changes when cells were exposed to 48 h of 1% oxygen, interferon gamma (IFN-γ), or both cues together. We specifically focused on changes in cell metabolism, immune modulation, extracellular matrix secretion and modification, and survival capacity. IFN-γ promoted expression of anti-pathogenic proteins and induced MSCs to limit inflammation and fibrosis while promoting their own survival. Hypoxia instead led to cell adaptation to low oxygen, including upregulation of proteins involved in anaerobic metabolism, autophagy, angiogenesis, and cell migration. While dual priming resulted in additive effects, we also found many instances of synergy. These data lend insight to how MSCs may behave after administration to a patient and suggest how priming cells beforehand could improve their therapeutic capacity.



https://ift.tt/2pS9oJU

Near infrared-emitting persistent luminescent nanoparticles for Hepatocellular Carcinoma imaging and luminescence-guided surgery

Publication date: June 2018
Source:Biomaterials, Volume 167
Author(s): Ting Ai, Wenting Shang, Hao Yan, Chaoting Zeng, Kun Wang, Yuan Gao, Tianpei Guan, Chihua Fang, Jie Tian
Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, is increasing nowadays and poses a serious threat to human health. However, if treated effectively and timely, it is clinically manageable or curable. Therefore, accurate detection and complete surgical resection remain priorities for HCC with a high potential of improving both survival and quality of life. Lacking of real-time guide technology, traditional surgery are usually relied on the subjective experience of surgeon, which have the limitation of high sensitivity detection tumor. Here, we developed a contrast agent, ZnGa2O4Cr0.004 (ZGC), used for guided surgery during operation to accurate delineation of HCC. ZGC showed excellent long-lasting afterglow properties that lasted for hours, which can aid in real-time guided surgery. Meanwhile, ZGC display high spatial resolution and deep penetration during pre-operation for diagnostic computed tomography (CT). Interestingly, we observed reverse imaging in the tumor region, known as a "dark hole", which further improves the contrast for surgery. This new multi-modality nanoparticle has great potential for accurate liver cancer imaging and resection guidance.

Graphical abstract

https://ift.tt/2uzhLPd

Nucleosome-inspired nanocarrier obtains encapsulation efficiency enhancement and side effects reduction in chemotherapy by using fullerenol assembled with doxorubicin

Publication date: June 2018
Source:Biomaterials, Volume 167
Author(s): Jinglong Tang, Ruirui Zhang, Mengyu Guo, Leihou Shao, Ying Liu, Yuliang Zhao, Suojiang Zhang, Yan Wu, Chunying Chen
Chemodrugs have been widely used to treat cancer; however, the chemotherapy usually leads to serious side effects and failure. Various nanomaterials and strategies have been explored for drug delivery to improve the efficacy of chemodrugs. One key to loading chemodrugs onto a nano-delivery system is enhancement of the encapsulation efficiency, especially for polymeric nanoparticles being loaded with hydrophilic drugs. Inspired by the ability of eukaryote to package millions of genes in the nucleus wrapping and condensing DNA around histones to form chromosomes, here we developed a karyon-like hybrid nanoparticle to achieve ultra-high encapsulation of doxorubicin (Dox) with reduced side effects. We utilized fullerenol as a "histone", packaged a great number of Dox, and used PEG-PLGA as the "karyotheca" coating the "nucleosome" (fullerenol and Dox complex) to stabilize the complex. It is noteworthy that the encapsulation efficiency of Dox in the polymeric micelles was increased from ∼5% to ∼79%. What's more, the biomimetic-inspired delivery system significantly reduced the chemodrug side effects by utilizing the radical scavenging ability of fullerenol. This novel drug-delivery design approach provides useful insights for improving the applicability of fullerenol in drug delivery systems for cancer therapy.

Graphical abstract

https://ift.tt/2pRTajM

Neonatal Transitions in Social Behavior and Their Implications for Autism

Publication date: Available online 30 March 2018
Source:Trends in Cognitive Sciences
Author(s): Sarah Shultz, Ami Klin, Warren Jones
Within the context of early infant–caregiver interaction, we review a series of pivotal transitions that occur within the first 6 months of typical infancy, with emphasis on behavior and brain mechanisms involved in preferential orientation towards, and interaction with, other people. Our goal in reviewing these transitions is to better understand how they may lay a necessary and/or sufficient groundwork for subsequent phases of development, and also to understand how the breakdown thereof, when development is atypical and those transitions become derailed, may instead yield disability. We review these developmental processes in light of recent studies documenting disruptions to early-emerging brain and behavior mechanisms in infants later diagnosed with autism spectrum disorder, shedding light on the brain–behavior pathogenesis of autism.



https://ift.tt/2uzAKsP

Interpreting and Utilising Intersubject Variability in Brain Function

Publication date: Available online 30 March 2018
Source:Trends in Cognitive Sciences
Author(s): Mohamed L. Seghier, Cathy J. Price
We consider between-subject variance in brain function as data rather than noise. We describe variability as a natural output of a noisy plastic system (the brain) where each subject embodies a particular parameterisation of that system. In this context, variability becomes an opportunity to: (i) better characterise typical versus atypical brain functions; (ii) reveal the different cognitive strategies and processing networks that can sustain similar tasks; and (iii) predict recovery capacity after brain damage by taking into account both damaged and spared processing pathways. This has many ramifications for understanding individual learning preferences and explaining the wide differences in human abilities and disabilities. Understanding variability boosts the translational potential of neuroimaging findings, in particular in clinical and educational neuroscience.



https://ift.tt/2pRrdc6

Measuring feeding difficulties in toddlers with Down syndrome

Publication date: 1 July 2018
Source:Appetite, Volume 126
Author(s): Marijn van Dijk, Wilma Lipke-Steenbeek
Early feeding problems occur frequently across the population, but have a higher incidence in children with Down syndrome (DS). Early identification can possibly be improved with the help of a valid screening instrument based on caregiver reports. In a previous study, we investigated the concurrent validity of the Dutch version of the Montreal Children's Hospital Feeding Scale (MCH-FS, SEP in Dutch) in a sample of typically developing toddlers, and we found a correlation between the score on the instrument and observed behavior during a regular meal. The current pilot study was a replication in a sample of children with DS (aged 1; 0–3; 0) and their primary caregivers (n = 32).The results showed that children in the sample did not score higher on the SEP than children in their respective norm groups. In addition, when caregivers reported more symptoms of feeding problems on the SEP, children showed more food refusal and negative affect during the observed meal. This suggests that the screening instrument is particularly associated with negative mealtime interactions. This is in contrast with earlier results, which mainly indicated a relation with eating skills.



https://ift.tt/2pRQpPs

Retraining of automatic action tendencies in individuals with obesity: A randomized controlled trial

Publication date: 1 July 2018
Source:Appetite, Volume 126
Author(s): Hannah Ferentzi, Hannah Scheibner, Reinout Wiers, Eni S. Becker, Johannes Lindenmeyer, Sylvia Beisel, Mike Rinck
Obesity is a major health concern, characterized by an automatically activated tendency to (over)-eat. Recent research suggests that an effective way to counteract automatic approach tendencies in unhealthy consumption behavior might be approach bias modification. Therefore, we investigated an approach-avoidance training for unhealthy food cues in 189 patients with obesity of a psychosomatic inpatient clinic who were participating in a nutrition advice program. Patients in the active training group were trained to make avoidance movements (pushing a joystick) in response to unhealthy food pictures and approach movements (pulling the joystick) in response to positive pictures, while the control group received sham training (approaching and avoiding both picture types). Approach-avoidance bias, body mass index, eating pathology and food-specific implicit associations were assessed before and after the training. In line with our hypothesis, approach-avoidance bias improved in the active training group after the training, in comparison to the sham training group. Moreover, this effect generalized to new, untrained stimuli. However, no effects of the training were found in a food-specific Single-Target Implicit Association Test, or on eating pathology questionnaires or body mass index. While the training results are promising, the effect of approach-avoidance bias modification on relevant behavior in obesity has yet to be established before it may be implemented as an add-on treatment.



https://ift.tt/2uxlSLR

Optimizing outcomes with polymethylmethacrylate fillers

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2GEPJqq

Étude de faisabilité de la spirométrie en médecine générale

Publication date: Available online 29 March 2018
Source:Revue des Maladies Respiratoires
Author(s): L. Bunge, D. Baruch, L. Plantier, T. Mazars, N. Roche, A. Izadifar
La bronchopneumopathie chronique obstructive est une maladie fréquente insuffisamment dépistée par les médecins généralistes (MG) alors que la spirométrie leur est accessible. L'objectif de ce travail était d'évaluer la qualité et l'interprétation des spirométries réalisées par des internes de médecine générale après une formation courte. Trois internes ont été formés pendant une demi-journée à la spirométrie. Dans 5 cabinets de médecine générale, une spirométrie était proposée à tous les fumeurs de plus de 35 ans. Les examens ont été relus en aveugle par un pneumologue expert indépendant pour évaluer leur qualité et leur interprétation. Des 184 patients éligibles, 89 % ont accepté de participer et 66 % (107) sont venus au 2^e rendez-vous. Le pneumologue a évalué la qualité des spirométries comme bonne pour 72 %, moyenne pour 20 % et non interprétable pour 8 %. L'interprétation était correcte pour 91 % des tests. Le coefficient Kappa de concordance de l'interprétation entre MG et expert était de 0,93. Ces tests ont permis de dépister des troubles ventilatoires obstructifs dans 17,5 % des cas. Le temps moyen d'une consultation avec spirométrie était de 19minutes. La consultation dédiée de spirométrie est bien acceptée par les patients en MG. Une formation courte reste à structurer pour permettre la réalisation et l'interprétation de spirométries en MG. Cette étude doit être étendue de façon à mieux étudier la reproductibilité en cas de courbe anormale.COPD is common but is under-diagnosed by general practitioners (GP). GP have a major role in the early diagnosis of this disease. GP could have access to spirometry. The aim of this study was to evaluate the quality and interpretation of spirometry performed by primary care residents following a short education session. Three residents were trained in spirometry for half a day. They then performed spirometry on all smokers over the age of 35 visiting five general practices. The results were reviewed blindly by an independent specialist pulmonologist to assess their quality and interpretation. Among 184 eligible patients, 89% agreed to participate and 66% (n=107) came for the second appointment. The pulmonologist evaluated the quality of spirometry as good in 72% of cases, of suboptimal but acceptable quality in 20% and of poor quality in 8%. Interpretation was accurate in 91% of tests. The Kappa concordance coefficient between GPs and the expert was 0.93. Airflow obstruction was detected in 17.5% of the screened subjects. The average time for a consultation with spirometry was 19minutes. The consultation dedicated to spirometry was well accepted by patients. A short training has to be structured to allow GPs to perform and interpret spirometry properly. This work needs to be extended to better assess reproducibility in cases of abnormal spirometry.



https://ift.tt/2GmJjbX

Influence of Class V preparation on in vivo temperature rise in anesthetized human pulp during exposure to a Polywave® LED light curing unit

Publication date: Available online 29 March 2018
Source:Dental Materials
Author(s): Driellen Christine Zarpellon, Patrício Runnacles, Cristiane Maucoski, Dayane Jaqueline Gross, Ulisses Coelho, Frederick Allen Rueggeberg, Cesar Augusto Galvão Arrais
ObjectiveThis in vivo study evaluated pulp temperature (PT) rise in human premolars having deep Class V preparations during exposure to a light curing unit (LCU) using selected exposure modes (EMs).MethodsAfter local Ethics Committee approval, intact first premolars (n=8) requiring extraction for orthodontic reasons, from 8 volunteers, received infiltrative and intraligamental anesthesia and were isolated using rubber dam. A minute pulp exposure was attained and sterile probe from a wireless, NIST-traceable, temperature acquisition system was inserted into the coronal pulp chamber to continuously monitor PT (°C). A deep buccal Class V preparation was prepared using a high speed diamond bur under air-water spray cooling. The surface was exposed to a Polywave^® LED LCU (Bluephase 20i, Ivoclar Vivadent) using selected EMs, allowing 7-min span between each exposure: 10-s in low (10-s/L), 10-s (10-s/H), 30-s (30-s/H), or 60-s (60-s/H) in high mode; and 5-s-Turbo (5-s/T). Peak PT values and PT increases over physiologic baseline levels (ΔT) were subjected to 1-way, repeated measures ANOVAs, and Bonferroni's post-hoc tests (α=0.05). Linear regression analysis was performed to establish the relationship between applied radiant exposure and ΔT.ResultsAll EMs produced higher peak PT than the baseline temperature (p<0.001). Only 60-s/H mode generated an average ΔT of 5.5°C (p<0.001). A significant, positive relationship was noted between applied radiant exposure and ΔT (r²=0.8962; p<0.001).SignificanceIn vivo exposure of deep Class V preparation to Polywave^® LED LCU increases PT to values considered safe for the pulp, for most EMs. Only the longest evaluated EM caused higher PT increase than the critical ΔT, thought to be associated with pulpal necrosis.



https://ift.tt/2IhX7Fv

Oxidative post-translational modification of βeta 2-glycoprotein I in the pathophysiology of the anti-phospholipid syndrome

Publication date: Available online 29 March 2018
Source:Free Radical Biology and Medicine
Author(s): James C. Weaver, Steven A. Krilis, Bill Giannakopoulos
The anti-phospholipid syndrome (APS) is a prothrombotic autoimmune disorder characterized by either thrombosis or pregnancy complications in the setting of persistent anti-phospholipid antibodies (aPL). βeta 2-glycoprotein I (β2-GPI) is the major autoantigen in APS that binds anionic phospholipids as well as specific receptors on platelets and endothelial cells resulting in activation of prothrombotic pathways. β2-GPI consists of 5 Domains that exist in a circular or linear form, with the latter occurring after binding to anionic phospholipids. β2-GPI also undergoes dynamic posttranslational modification between oxidized and free thiol forms. The relationship between posttranslational modification and structural conformation is yet to be definitively clarified. Compared with controls, patients with the APS have higher levels of total β2-GPI and lower levels of free thiol β2-GPI. This raises the possibility of using quantification of β2-GPI posttranslational modification as a redox biomarker in the management and diagnosis of the APS.

Graphical abstract

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Concomitant BCORL1 and BRAF Mutations in Vemurafenib-Resistant Melanoma Cells

Publication date: May 2018
Source:Neoplasia, Volume 20, Issue 5
Author(s): Luca Mologni, Mariantonia Costanza, Geeta Geeta Sharma, Michela Viltadi, Luca Massimino, Stefania Citterio, Stefania Purgante, Hima Raman, Alessandra Pirola, Massimo Zucchetti, Rocco Piazza, Carlo Gambacorti-Passerini
BRAF is the most frequently mutated gene in melanoma. Constitutive activation of mutant BRAF^V600E leads to aberrant Ras-independent MAPK signaling and cell transformation. Inhibition of mutant BRAF is a current frontline therapy for such cases, with improved survival compared with chemotherapy. Unfortunately, reactivation of MAPK signaling by several mechanisms has been shown to cause drug resistance and disease recurrence. In this work, we describe the co-occurrence of an in-frame deletion within an amplified BRAF^V600E locus and a missense point mutation of the transcriptional repressor BCORL1 in vemurafenib-resistant A375 melanoma cells. Functional data confirmed that truncated p47BRAF^V600E and mutant BCORL1^Q1076H both contribute to resistance. Interestingly, either endogenous BCORL1 silencing or ectopic BCORL1^Q1076H expression mimicked the effects of a CRISPR/Cas9-edited BCORL1^Q1076H locus, suggesting a complex mixture of loss- and gain-of-function effects caused by the mutation. Transcriptomic data confirmed this hypothesis. Finally, we show that the pan-RAF inhibitor sorafenib is not affected by expression of BRAF deletion variant and effectively synergizes with vemurafenib to block resistant cells, suggesting a possible intervention for this class of mutants.



https://ift.tt/2pRCl8D

Combined Inhibition of ATR and WEE1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer

Publication date: May 2018
Source:Neoplasia, Volume 20, Issue 5
Author(s): Juan Jin, Hehui Fang, Fang Yang, Wenfei Ji, Nan Guan, Zijia Sun, Yaqin Shi, Guohua Zhou, Xiaoxiang Guan
Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that poses a clinical challenge. Thus, new therapy strategies are urgently needed. The selective WEE1 inhibitor, AZD1775, has shown strong anti-proliferative effects on a variety of tumors. Here, we first demonstrate that inhibition of ATR by selective inhibitor AZD6738 can enhance AZD1775-caused growth inhibition in TNBC. Our results show that the enhanced cell death is attributed to repressed DNA damage repair and excessive replication stress, thereby causing increased DNA damage reflected by accumulation of the DNA double-strand-break marker γH2AX. On the other hand, combined treatment with AZD6738 and AZD1775 forces mitotic entry of cells with DNA damages by activating CDK1 activity, inducing severely aberrant mitosis and mitotic catastrophe, ultimately resulting in cell death. Dual inhibition of WEE1 and ATR also inactivated RAD51-mediated homologous recombination, which sensitized TNBC cells to cisplatin and PARP inhibitor. Here, based on the preclinical results that ATR inhibition synergizes with WEE1 inhibition in TNBC, we propose that this combination therapy alone, or in parallel with chemotherapy, represents an innovative and potent targeted therapy in TNBC.



https://ift.tt/2uExbl8

Adiponectin Reverses the Proliferative Effects of Estradiol and IGF-1 in Human Epithelial Ovarian Cancer Cells by Downregulating the Expression of Their Receptors

Abstract

The expression of adiponectin receptors AdipoR1 and AdipoR2 has been reported in the human ovary and ovarian cancer tissues. Moreover, adiponectin has been reported to act as an anti-tumor factor by inhibiting cancer cell proliferation. Thus, we investigate whether adiponectin and its receptors influence ovarian cancer development. In the present study, we found that adiponectin was not expressed in the granulosa cell line (COV434), and epithelial ovarian cancer cell lines (OVCAR-3, SKOV-3, and Caov-3). Additionally, we found that AdipoR1 and AdipoR2 expression is lower in epithelial ovarian cancer cells than in granulosa tumor cells. Endogenous 17β-estradiol as well as exogenous estrogens, such as bisphenol A and its chlorinated and brominated analogs do not affect adiponectin receptor expression. We found that adiponectin inhibited the growth of OVCAR-3 and SKOV-3 cells, and that this effect was independent of apoptosis. Moreover, adiponectin reverses the stimulatory effects of 17β-estradiol and insulin-like growth factor 1 on cell proliferation by downregulating the expression of their receptors, whereas progesterone increased the sensitivity of cancer cells to adiponectin by upregulating AdipoR1 and AdipoR2 expression. These results suggest interactions between adiponectin and various ovarian steroid hormone and growth factor pathways in ovarian cancer cells.

https://ift.tt/2GGtlg8

Agraphia with reversible splenial corpus callosum lesion caused by hypoglycemia

Publication date: Available online 30 March 2018
Source:Brain and Development
Author(s): Yukari Miyakawa, Tatsuo Fuchigami, Masako Aoki, Yusuke Mine, Junichi Suzuki, Tatsuhiko Urakami, Shori Takahashi
BackgroundNeurological manifestations caused by hypoglycemia range from reversible focal deficits and transient encephalopathy to irreversible coma or death. Recently, high signal intensity lesions in the splenium of the corpus callosum on diffusion-weighted magnetic resonance imaging were reported in adults experiencing hypoglycemia. However, patients presenting with agraphia are rare.Subject and methodsWe examined a 17-year-old left-handed female patient with type 1 diabetes who exhibited transient left agraphia with a reversible splenium lesion of the corpus callosum on diffusion-weighted imaging caused by hypoglycemia, which was improved with blood glucose management alone.ConclusionThis rare case indicates that agraphia, a sign of callosal disconnection syndrome, can result from a reversible splenial lesion of the corpus callosum caused by hypoglycemia.



https://ift.tt/2J6BTeR

Accelerated Long-Term Forgetting and Behavioural Difficulties in Children with Epilepsy

Publication date: Available online 30 March 2018
Source:Cortex
Author(s): Michael B. Gascoigne, Mary Lou Smith, Belinda Barton, Richard Webster, Deepak Gill, Suncica Lah
Patients with epilepsy have been shown to exhibit a range of memory deficits, including the rapid forgetting of newly-learned material over long, but not short, delays (termed accelerated long-term forgetting; ALF). Behavioural problems, such as mood disorders and social difficulties, are also overrepresented among children with epilepsy, when compared to patients with other chronic diseases and the general population. We investigated whether ALF was associated with behavioural or psychosocial deficits in children with epilepsy. Patients with either idiopathic generalised epilepsy (IGE; n = 20) or temporal lobe epilepsy (TLE; n = 23) and healthy controls (n = 53) of comparable age, sex, and socioeconomic status completed a battery of neuropsychological tests, including a list-learning task that required recall after short (30-min) and long (7-day) delays. Parents or guardians of all participants also completed the Child Behavior Checklist (CBCL). Compared to control participants, patients with IGE and TLE had higher scores on all but one of the indices of behavioural problems. When patients with IGE and TLE were merged into a single group, they were found to have negative correlations between 7-day recall and internalising, social and total problem behaviour domains, where poorer 7-day recall was associated with behavioural problems of greater severity. These findings suggest that impaired episodic recall is associated with behavioural deficits, including social problems, which are routinely observed in patients with epilepsy.



https://ift.tt/2IhyBUL

Knowledge about writing influences reading: Dynamic visual information about letter production facilitates letter identification

Publication date: Available online 30 March 2018
Source:Cortex
Author(s): Teresa Schubert, Caroline Reilhac, Michael McCloskey
How are reading and writing related? In this study, we address the relationship between letter identification and letter production, uncovering a link in which production information can be used to identify letters presented dynamically. By testing an individual with a deficit in letter identification, we identified a benefit which would be masked by ceiling effects in unimpaired readers. In Experiment 1 we found that letter stimuli defined by the direction of dot motion (tiny dots within letter move leftward, background dots move rightward) provided no advantage over static letters. In Experiment 2, we tested dynamic stimuli in which the letter shapes emerged over time: drawn as they would be written, drawn in reverse, or with the letter shape filled in randomly. Improved identification was observed only for letters drawn as they are typically written. These results demonstrate that information about letter production can be integrated into letter identification, and point to bi-directional connections between stored letter production information (used for writing) and abstract letter identity representations (used in both reading and writing). The links from stored production information to abstract letter identities allow the former to activate the latter. We also consider the implications of our results for remediation of acquired letter identification deficits, including letter-drawing treatments and the underlying cause of their efficacy.



https://ift.tt/2GGm2p4

Cognitive and functional correlates of accelerated long-term forgetting in temporal lobe epilepsy

Publication date: Available online 30 March 2018
Source:Cortex
Author(s): Samantha Audrain, Mary Pat McAndrews
While we know that hippocampal dysfunction is responsible for the memory deficits that patients with temporal lobe epilepsy exhibit at relatively short study-test delays, the role of this region in accelerated long-term forgetting (ALF) is not yet clear. In the present study, we probed the role of the hippocampus in ALF by directly comparing memory for associations to memory that could be supported by item recognition during a forced choice recognition task over delays ranging from 15-minutes to 72-hours. We additionally examined resting-state functional connectivity between the hippocampus and cortical regions known to be involved in processing these types of stimuli, as well as the relationship between ALF and various clinical variables including structural abnormality in the hippocampus, lateralization of epileptic focus, presence of seizures across the retention period, and standardized composite memory scores. We found evidence of accelerated forgetting for item stimuli (but not associative stimuli) by 6 hours post-learning, which became statistically reliable by 72-hours. This finding suggests that unlike controls, patients were unable to utilize novelty to reject the incorrect object-scene pair. While none of the examined clinical variables were related to long-term forgetting, reduced resting-state functional connectivity between the affected anterior hippocampus and unaffected lateral temporal cortex predicted forgetting of item stimuli over the 72-hour delay. Implications for the role of the hippocampus in accelerated long-term forgetting, and existing theories of systems consolidation in this context are discussed.



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Parallel reaction monitoring on a Q Exactive mass spectrometer increases reproducibility of phosphopeptide detection in bacterial phosphoproteomics measurements

Publication date: Available online 29 March 2018
Source:Journal of Proteomics
Author(s): Christoph Taumer, Lena Griesbaum, Alen Kovacevic, Boumediene Soufi, Nicolas C. Nalpas, Boris Macek
Increasing number of studies report the relevance of protein Ser/Thr/Tyr phosphorylation in bacterial physiology, yet the analysis of this type of modification in bacteria still presents a considerable challenge. Unlike in eukaryotes, where tens of thousands of phosphorylation events likely occupy more than two thirds of the proteome, the abundance of protein phosphorylation is much lower in bacteria. Even the state-of-the-art phosphopeptide enrichment protocols fail to remove the high background of abundant unmodified peptides, leading to low signal intensity and undersampling of phosphopeptide precursor ions in consecutive data-dependent MS runs. Consequently, large-scale bacterial phosphoproteomic datasets often suffer from poor reproducibility and a high number of missing values. Here we explore the application of parallel reaction monitoring (PRM) on a Q Exactive mass spectrometer in bacterial phosphoproteome analysis, focusing especially on run-to-run sampling reproducibility. In multiple measurements of identical phosphopeptide-enriched samples, we show that PRM outperforms data-dependent acquisition (DDA) in terms of detection frequency, reaching almost complete sampling efficiency, compared to 20% in DDA. We observe a similar trend over multiple heterogeneous phosphopeptide-enriched samples and conclude that PRM shows a great promise in bacterial phosphoproteomics analyses where reproducible detection and quantification of a relatively small set of phosphopeptides is desired.SignificanceBacterial phosphorylated peptides occur in low abundance compared to their unmodified counterparts, and are therefore rarely reproducibly detected in shotgun (DDA) proteomics measurements. Here we show that parallel reaction monitoring complements DDA analyses and makes detection of known, targeted phosphopeptides more reproducible. This will be of significance in replicated MS measurements that have a goal to reproducibly detect and quantify phosphopeptides of interest.



https://ift.tt/2J48wK6

Proteomic analysis revealed proteins induced upon Azotobacter vinelandii encystment

Publication date: Available online 29 March 2018
Source:Journal of Proteomics
Author(s): Sangita Chowdhury-Paul, Victoria Pando-Robles, Verónica Jiménez-Jacinto, Daniel Segura, Guadalupe Espín, Cinthia Núñez

Graphical abstract

https://ift.tt/2E6zvB9

The mechanisms of Ag85A DNA vaccine activates RNA sensors through new signal transduction

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Jingbo Zhai, Qiubo Wang, Yunfeng Gao, Ran Zhang, Shengjun Li, Bing Wei, Yong You, Xun Sun, Changlong Lu
Low immunogenicity is one of the major problems limiting the clinical use for DNA vaccines, which makes it impossible to obtain a strong protective immune response after vaccination. In order to explore whether Ag85A DNA vaccine could mount more efficiently protective immune response through new RNA sensor and its signal transduction pathway of antigen presentation we designed and synthesized Ag85A gene fragment containing multiple points mutations and transfected the gene fragment into the dendritic cell line (DC2.4) by CRISPR/Cas9. Subsequently, we focused on the changes of RNA sensors RIG-I, Mda-5, and the downstream adaptors MAVS, IRF3, IRF7 and IFN-β. The results indicated the significant increases in the mRNA and protein expression of RNA sensors RIG-I, Mda-5 and related adaptors MAVS, IRF3, IRF7, and IFN-β in the mutant DC 2.4 cells. The flow cytometry results demonstrated that the expression of MHC II on the surface of DC 2.4 significantly increased when compared with that in control. Therefore, it is suggested that Ag85A mutant DNA could release immunogenic message through RNA sensors and related adaptors via non protein pathway. There is at least one RNA signal transduction pathway of Ag85A DNA in DC2.4 cell. The work provides a new mode of action for nucleic acid vaccine to improve immunogenicity and meaningful data for the better understanding of the mechanisms of DNA vaccine.



https://ift.tt/2E7iBlR

Long-term administration of pDC-Stimulative Lactococcus lactis strain decelerates senescence and prolongs the lifespan of mice

Publication date: May 2018
Source:International Immunopharmacology, Volume 58
Author(s): Tetsu Sugimura, Kenta Jounai, Konomi Ohshio, Hiroaki Suzuki, Takayoshi Kirisako, Yoshihiko Sugihara, Daisuke Fujiwara
The decline in immune function caused by aging increases the risk of infectious diseases, tumorigeneses and chronic inflammation, resulting in accelerating senescence. We previously reported a lactic acid bacteria, Lactococcus lactis strain Plasma (synonym of Lactococcus lactis subsp. lactis JCM 5805, Lc-Plasma), that stimulates plasmacytoid dendritic cells (pDCs), which play a crucial role in phylaxis from viral infection. In this study, we investigated the anti-aging effects of long-term oral administration of Lc-Plasma in a senescence-accelerated mouse strain, SAMP6. Mice given Lc-Plasma showed a significant improvement in survival rate at 82 weeks and a decreased senescence score as compared with control mice throughout this study. Anatomic analysis at 82 weeks revealed that the frequency of altered hepatocellular foci was significantly lower, and the incidence of other pathological findings in the liver and lungs tended to be lower in Lc-Plasma mice than in control mice. Transcription level of the IL-1β gene in lungs also tended to be lower in Lc-Plasma mice. Furthermore, the thinning of skin and age-related decrease in muscle mass were also significantly suppressed in the Lc-Plasma group as compared with the control group. Consistent with these phenotypic features, pDCs activity was significantly higher in Lc-Plasma mice than in control mice. In conclusion, long-term administration of Lc-Plasma can decelerate senescence and prolong lifespan via maintenance of the immune system due to activation of pDCs.



https://ift.tt/2J46Joe

Effect of ulixertinib, a novel ERK1/2 inhibitor, on the QT/QTc interval in patients with advanced solid tumor malignancies

Abstract

Purpose

The aim of this analysis was to investigate the potential for ulixertinib (BVD-523) to prolong cardiac repolarization. The mean prolongation of the corrected QT (QTc) interval was predicted at the mean maximum drug concentrations of the recommended phase 2 dose (RP2D; 600 mg BID) and of higher concentrations. In addition, the effect of ulixertinib on other quantitative ECG parameters was assessed.

Methods

In a two-part, phase 1, open-label study in adults with advanced solid tumors, 105 patients [24 in Part 1 (dose escalation) and 81 in Part 2 (cohort expansion)] were included in a QT prolongation analysis. Electrocardiograms (ECGs) extracted from 12-lead Holter monitors, along with time-matched pharmacokinetic blood samples, were collected over 12 h on cycle 1 day 1 and cycle 1 day 15 and analyzed by a core ECG laboratory.

Results

A small increase in heart rate was observed on both study days (up to 5.6 bpm on day 1 and up to 7 bpm on day 15). The estimated mean changes from baseline in the study-specific QTc interval (QTcSS), at the ulixertinib C_max, were − 0.529 ms (90% CI − 6.621, 5.562) on day 1 and − 9.202 ms (90% CI − 22.505, 4.101) on day 15. The concentration: QTc regression slopes were mildly positive but not statistically significant [0.53 (90% CI − 1.343, 2.412) and 1.16 (90% CI − 1.732, 4.042) ms per µg/mL for days 1 and 15, respectively]. Ulixertinib had no meaningful effect on PR or QRS intervals.

Conclusions

Ulixertinib administered to patients with solid tumors at clinically relevant doses has a low risk for QT/QTc prolongation or any other effects on ECG parameters.

Registration

The study is registered at Clinicaltrials.gov (NCT01781429) and was sponsored by BioMed Valley Discoveries.

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Cardiotoxic effects of chemotherapy: A review of both cytotoxic and molecular targeted oncology therapies and their effect on the cardiovascular system

Publication date: Available online 29 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Hani M Babiker, Ali McBride, Michael Newton, Leigh M. Boehmer, Adrienne Goeller Drucker, Mollie Gowan, Manouchkathe Cassagnol, Todd D. Camenisch, Faiz Anwer, James M. Hollands
Cardiotoxic effects of chemotherapy and targeted drugs are ubiquitous and challenging in the field of oncology therapeutics. The broad spectrum of toxicities ranging from ischemic, hypertensive, cardiomyopathic, and arrhythmic complications can present as a significant challenge for clinicians treating cancer patients. If early diagnosis and intervention of cardiotoxic complications is missed, this can lead to delay or abrogation of planned treatment, which can potentially culminate to significant morbidity due to not only the cardiotoxic complications but also the progression of cancer. Hence, full knowledge of cardiovascular complications of chemotherapeutic agents, essential diagnostics tests to order, and appropriate management is paramount to oncologist, oncology pharmacists, and scientific clinical investigators. The aforementioned is particularly true in the current oncology era of plenteous early clinical trials studying several pathway/molecular-targeting agents with an increased cardiotoxic potential and the rapid expedited approval of those drugs by the FDA. Herein, we present a review discussing cardiotoxic effects of drugs and guidelines for management of the toxicities to assist the medical field in general managing patients with cancer.



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Going the distance: are we losing patients along the multiple myeloma treatment pathway?

Publication date: Available online 29 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Evangelos Terpos, Florence Suzan, Hartmut Goldschmidt
Despite data suggesting that individuals with multiple myeloma can benefit from receiving several lines of therapy, and guidelines recommending treatment after relapse, a recent European patient chart review found that only 61% of patients receive second-line treatment. The review found that factors such as old age and previous adverse events lead to physicians deciding not to treat after relapse. However, given the large number of regimens available, treatment can be tailored to individual patients' needs and supportive care measures can help with the management of adverse effects. If approved therapies are not suitable for a patient, guidelines recommend registration in a clinical trial, yet only 7% of patients in the review were participating in such studies. A need for better education on the range of treatments available and their risk–benefit profiles is suggested. Access to new drugs should be examined to maximise the number of patients benefitting from them.



https://ift.tt/2uvFuA0

Role of Bevacizumab in Uterine Leiomyosarcoma

Publication date: Available online 29 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Giorgio Bogani, Antonino Ditto, Fabio Martineli, Mauro Signorelli, Valentina Chiappa, Caterina Fonatella, Roberta Sanfilippo, Umberto Leone Roberti Maggiore, Simone Ferrero, Domenica Lorusso, Francesco Raspagliesi
In the recent years, angiogenetic inhibitors have emerged for the treatment of several malignancies. In particular, bevacizumab has proved to be effective in many types of cancers (including sarcoma), but the limitations of antiangiogenic therapy have been shown in practice. Here, we sought to review the current evidence on the role and efficacy of bevacizumab in patients affected by uterine leiomyosarcoma. On April 2017, Literature was searched in order to identify studies reporting outcomes of patients affected either by early stage or advanced/recurred uterine leiomyosarcoma undergoing treatment with bevacizumab, alone or in combination with other chemotherapeutic regimens. Searching the literature data of 69 patients affected by metastatic, unresectable uterine leiomyosarcoma were retrieved; on the contrary, no data regarding the use of bevacizumab in patients with early-stage uterine leiomyosarcoma was published. Current evidence suggested that the addiction of bevacizumab to standard treatment modality does not increase grade 3 or worse toxicity (assessed by CTCAE). Pooled data regarding response rate suggested that 35%, 28%, 26% and 11% of patients experienced objective cure (complete + partial response), stable disease, progressive disease and unknown response, respectively. Data from the only one randomized controlled trial suggested that objective cure rate does not differ from standard chemotherapy treatment, thus limiting the indication to add bevacizumab in patients affected by metastatic, unresectable uterine leiomyosarcoma. The current evidence does not justify the use of bevacizumab into clinical practice. Further randomized studies testing the role of bevacizumab are warranted.



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Genetic alterations crossing the borders of distinct hematopoetic lineages and solid tumors: Diagnostic challenges in the era of high-throughput sequencing in hemato-oncology

Publication date: Available online 29 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Evgenii Shumilov, Johanna Flach, Thomas Pabst, Martin Fiedler, Anne Angelillo-Scherrer, Lorenz Trümper, Raphael Joncourt, Alexander Kohlmann, Ulrike Bacher
Owing to the introduction of next-generation sequencing (NGS) new challenges for diagnostic algorithms and the interpretation of the results for therapeutic decision making in hemato-oncology have arisen. Recurrent somatic mutations crossing the borders between different hematological entities and solid neoplasms have been detected. In analogy to mutant TP53, the same mutation type may occur in myeloid, B- or T-lymphatic malignancies or solid neoplasms. At the same time, a certain mutation can show different prognostic outcomes in different entities and co-existence of certain mutations may change the prognostic relevance. These insights may spark the investigation of targeted therapies with the same substances across different disease entities. This review article summarizes mutations that can emerge in different hematologic and solid malignancies and summarizes other obstacles in the era of modern molecular diagnostics, such as the phenomenon of "clonal hematopoiesis of indeterminate potential" being difficult to interpret in the individual patient.



https://ift.tt/2uvFbVS

Prognostic and Predictive Factors in Patients with Brain Metastases from Solid Tumors: A Review of Published Nomograms

Publication date: Available online 29 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Carsten Nieder, Minesh P. Mehta, Hans Geinitz, Anca L. Grosu
ObjectiveTo review published nomograms that predict endpoints such as overall survival (OS) or risk of intracranial relapse in patients with brain metastases from solid tumors.MethodsThe methods and results of nomogram studies identified by a systematic search were extracted and compared, stratified by endpoint predicted by the respective nomograms. In particular, validation strategies (external/internal), concordance indices (cut-off 0.75) and comparisons to older models were analyzed.ResultsSix publications reported on prediction of OS. Most of these analyses focused on one particular primary tumor site, e.g., breast cancer or hepatocellular carcinoma, while the largest study included different primary tumor sites. The median number of patients was 244. Three of six studies included external validation cohorts. With few exceptions, concordance indices <0.75 were reported. In all studies reporting this endpoint, the nomogram outperformed older prognostic scores. Two nomograms focused on development of new brain metastases after radiosurgery (one externally validated), one on survival free from salvage whole brain radiotherapy (WBRT) after radiosurgery, and one on neurologic and non-neurologic death in patients receiving radiosurgery after WBRT failure. All concordance indices of these 4 nomograms were <0.70.ConclusionTaking into account concordance indices and comparisons to older prognostic models, the most promising, externally validated nomograms are the breast cancer and the non-small cell lung cancer nomogram predicting OS, and the distant brain failure after radiosurgery nomogram. Additional validation studies as well as continuous monitoring of the models' performance appear necessary to ensure their clinical applicability in the present era of rapidly changing treatment paradigms.



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Sarcoma–The Standard-bearer in cancer discovery

Publication date: Available online 29 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Jared W. Potter, Kevin B. Jones, Jared J. Barrott
Sarcoma is a rare tumor type that occurs most frequently in connective tissue. Despite its uncommon occurrence, sarcoma research has provided the means for groundbreaking research that has advanced our understanding of general cancer mechanisms. It is through sarcoma research that the pioneering efforts of cancer immunotherapy were explored, that we understand the inherent genetic nature of cancer mutations, and that we appreciate the subclassification of general cancer types to make more accurate prognoses. This review explores the brief history of sarcoma research and what sarcomas can still teach us about the future of cancer research, especially in regard to novel immunotherapy targets, the role of epigenetics in disease progression and chemoresistance, and the benefits of more focused clinical trials.



https://ift.tt/2E7QIKl

How to treat whiteheads on the nose

Whiteheads are stubborn acne lesions that develop just under the skin. The nose is a common site for whiteheads to form, as this part of the face produces a lot of oil and is touched frequently throughout the day. We look at several ways to treat whiteheads on the nose, as well as how to prevent them in the future.

https://ift.tt/2GlOxF6

Identification of Generalist Registered Dietitian Nutritionist Knowledge Gaps in Diabetes Medical Nutrition Therapy Compared to Diabetes-Credentialed Registered Dietitian Nutritionists: Results of a Survey to Inform Educational Opportunities

Publication date: Available online 29 March 2018
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Kimberly Bisanz, Anna Parker, Cecily Byrne, Sandra A. Parker, Joan Thomas, Juliet Mancino, Rosa K. Hand




https://ift.tt/2uvJn7X

Cultivating the Desire to Mentor in Dietetic Interns

Publication date: Available online 29 March 2018
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Nina Roofe, Alicia Landry




https://ift.tt/2GYJzPx

Impact of formulation on the iontophoretic delivery of the FOLFIRINOX regimen for the treatment of pancreatic cancer

Abstract

Purpose

Effective treatment of patients with locally advanced pancreatic cancer is a significant unmet clinical need. One major hurdle that exists is inadequate drug delivery due to the desmoplastic stroma and poor vascularization that is characteristic of pancreatic cancer. The local iontophoretic delivery of chemotherapies provides a novel way of improving treatment. With the growing practice of highly toxic combination therapies in the treatment of pancreatic cancer, the use of iontophoresis for local delivery can potentiate the anti-cancer effects of these therapies while sparing unwanted toxicity. The objective of this study was to investigate the impact of formulation on the electro-transport of the FOLFIRINOX regimen for the development of a new treatment for pancreatic cancer.

Methods

Three formulations of the FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) were generated at a fixed pH of 6.0 and were referred to as formulation A (single drug solution with all four drugs combined), formulation B (two drug solutions with two drugs per solution), and formulation C (four individual drug solutions). Anodic iontophoresis of the three different formulations was evaluated in orthotopic patient-derived xenografts of pancreatic cancer.

Results

Iontophoretic transport of the FOLFIRINOX drugs was characterized according to organ exposure after a single device treatment in vivo. We report that the co-iontophoresis of two drug solutions, leucovorin + oxaliplatin and 5-fluorouracil + irinotecan, resulted in the highest levels of cytotoxic drugs in the tumor compared to drugs delivered individually or combined into one solution. There was no significant difference in plasma, pancreas, kidney, and liver exposure to the cytotoxic drugs delivered by the three different formulations. In addition, we found that reducing the duration of iontophoretic treatment from 10 to 5 min per solution resulted in a significant decrease in drug concentrations.

Conclusions

Underlying the difference in drug transport of the formulations was electrolyte concentrations, which includes both active and inactive components. Electrolyte concentrations can hinder or improve drug electro-transport. Overall, balancing electrolyte concentration is needed for optimal electro-transport.

https://ift.tt/2pTCUho