Heart irradiation reduces microvascular density and accumulation of HSPA1 in mice

Abstract

Purpose

Improvement of radiotherapy techniques reduces the exposure of normal tissues to ionizing radiation. However, the risk of radiation-related late effects remains elevated. In the present study, we investigated long-term effects of radiation on heart muscle morphology.

Materials and methods

We established a mouse model to study microvascular density (MVD), deposition of collagen fibers, and changes in accumulation of heat shock 70 kDa protein 1 (HSPA1) in irradiated heart tissue. Hearts of C57BL/6 mice received a single dose of X‑ray radiation in the range 0.2–16 Gy. Analyses were performed 20, 40, and 60 weeks after irradiation.

Results

Reduction in MD was revealed as a long-term effect observed 20–60 weeks after irradiation. Moreover, a significant and dose-dependent increase in accumulation of HSPA1, both cytoplasmic and nuclear, was observed in heart tissues collected 20 weeks after irradiation. We also noticed an increase in collagen deposition in hearts treated with higher doses.

Conclusions

This study shows that some changes induced by radiation in the heart tissue, such as reduction in microvessel density, increase in collagen deposition, and accumulation of HSPA1, are observed as long-term effects which might be associated with late radiation cardiotoxicity.

http://ift.tt/2z33Gen

Double fluorescent labelling of a bipolar epithelial cell in vitro: The outer hair cell

Publication date: 1 January 2018
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Csaba Harasztosi, Entcho Klenske, Susanne Badum, Emese Harasztosi, Anthony W. Gummer
BackgroundFluorescence membrane markers are efficient tools for visualizing the dynamics of membrane recycling processes in living cells. The outer hair cell (OHC) − a bipolar epithelial cell in the cochlea − possesses endocytic activity at both its apical and basal poles. The best visual overview of transcytosis in the OHC is achieved when the cell is isolated, so that both the apical and the basal poles are in the same focal plane to allow confocal imaging. Until now, fluorescent markers were applied to the extracellular environment of isolated OHCs without distinguishing the apical and basal poles. The drawback of that configuration is that apicobasal and basoapical vesicle traffic labelled at the opposite poles cannot be visualized independently because the same fluorescent marker has access to both poles.New methodA double-barrel, capillary perfusion system was developed to independently stain either one pole or both the apical and the basal poles of isolated OHCs using different types of fluorescence membrane markers.ResultsProducing laminar fluid flow, the double-barrel perfusor allows investigation of the dynamics of apicobasal and basoapical vesicle traffic independently and/or simultaneously in the same OHC.Comparison with existing methodThis method offers a unique option for investigating bidirectional vesicle traffic in bipolar epithelial cells, which is superior to other already established labelling techniques.ConclusionsThe double-barrel perfusion system, suitable for selectively staining a longitudinal section of the plasma membrane of an isolated bipolar epithelial cell, opens new possibilities for investigating cell labelling and intracellular vesicle traffic.

Graphical abstract

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Functional brain connectivity in resting-state fMRI using phase and magnitude data

Publication date: 1 January 2018
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Zikuan Chen, Arvind Caprihan, Eswar Damaraju, Srinivas Rachakonda, Vince Calhoun
BackgroundThe output of BOLD fMRI consists of a pair of magnitude and phase components. While the magnitude data has been widely accepted for brain function analysis, we can also make use of the phase data (unwrapped) since this is a good representation of the internal magnetic field. In this work, we discuss the use of fMRI phase data for brain function analysis.New methodsThe fMRI phase data taken from 100 subjects are preprocessed using standard SPM approaches. Group independent component analysis (ICA) is applied to the magnitude and phase data separately. We then compare the spatial patterns for both magnitude and phase data using an empirical spatial smoothing procedure. We also evaluate the magnitude and phase functional network connectivity (FC) matrices.ResultsWe observed the positive/negative correlation-balanced functional connectivity in phase data, which is distinct from the positive correlation prevalence in magnitude data. The phase FC (pFC) structure is quite different from the magnitude FC (mFC) in functional clusters (on-diagonal blocks or cliques) and inter-cluster couplings (off-diagonal blocks).Comparison with existingMethods since both the magnitude and phase data of the fMRI signals are generated from the same magnetic source, either can be useful for brain function analysis from different perspective (per different measurements). Herein, we report on making use of resting-state fMRI phase data for brain functional analysis in comparison with magnitude data. This exploration in phase fMRI may provide a new arena for more comprehensive brain function analysis.

Graphical abstract

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Combined effects of binary antibiotic mixture on growth, microcystin production, and extracellular release of Microcystis aeruginosa : application of response surface methodology

Abstract

The interactive effects of binary antibiotic mixtures of spiramycin (SP) and ampicillin (AMP) on Microcystis aeruginosa (MA) in terms of growth as well as microcystin production and extracellular release were investigated through the response surface methodology (RSM). SP with higher 50 and 5% effective concentrations in MA growth was more toxic to MA than AMP. RSM model for toxic unit approach suggested that the combined toxicity of SP and AMP varied from synergism to antagonism with SP/AMP mixture ratio decreasing from reversed equitoxic ratio (5:1) to equitoxic ratio (1:5). Deviations from the prediction of concentration addition (CA) and independent action (IA) model further indicated that combined toxicity of target antibiotics mixed in equivalent ratio (1:1) varied from synergism to antagonism with increasing total dose of SP and AMP. With the increase of SP/AMP mixture ratio, combined effect of mixed antibiotics on MA growth changed from stimulation to inhibition due to the variation of the combined toxicity and the increasing proportion of higher toxic component (SP) in the mixture. The mixture of target antibiotics at their environmentally relevant concentrations with increased total dose and SP/AMP mixture ratio stimulated intracellular microcystin synthesis and facilitated MA cell lysis, thus leading to the increase of microcystin productivity and extracellular release.

http://ift.tt/2h2UwUF

Isolation and characterization of culturable bacteria present in the spent nuclear fuel pool water

Abstract

A spent nuclear fuel (SNF) pool is a key facility for safe management of nuclear waste, where spent nuclear fuel rods are stored in a water pool. The spent fuel rods carry a significant amount of radioactivity; they are either recycled or stored for further processing. Pool water acts as a heat sink as well as a shield against the radiation present in spent/burned fuel rods. The water used in these pools is filtered by an ultra-filtration process which makes certain the purity of water. As the life span of these pools is approximately 20 to 40 years, the maintenance of pure water is a big challenge. A number of researchers have shown the presence of bacterial communities in this ultrapure water. The bacterial types present in SNF pool water is of increasing interest for their potential bioremediation applications for radioactive waste. The present study showed the isolation of six bacterial species in the SNF pool water samples, which had significant radio-tolerance (D₁₀ value 248 Gy to 2 kGy) and also biofilm-forming capabilities. These strains were also investigated for their heavy metal removal capacity. Maximum biofilm-mediated heavy metal (Co and Ni) removal (up to 3.8 μg/mg of biomass) was observed by three isolates (FPB1, FPB4, and FPB6). The ability of these bacterial isolates to survive in radioactive environments can be of great interest for remediation of radioactive contaminants.

http://ift.tt/2zxw70e

Prokaryotic community profiling of local algae wastewaters using advanced 16S rRNA gene sequencing

Abstract

Algae biomass-fed wastewaters are a promising source of lipid and bioenergy manufacture, revealing substantial end-product investment returns. However, wastewaters would contain lytic pathogens carrying drug resistance detrimental to algae yield and environmental safety. This study was conducted to simultaneously decipher through high-throughput advanced Illumina 16S ribosomal RNA (rRNA) gene sequencing, the cultivable and uncultivable bacterial community profile found in a single sample that was directly recovered from the local wastewater systems. Samples were collected from two previously documented sources including anaerobically digested (AD) municipal wastewater and swine wastewater with algae namely Chlorella spp. in addition to control samples, swine wastewater, and municipal wastewater without algae. Results indicated the presence of a significant level of Bacteria in all samples with an average of approximately 95.49% followed by Archaea 2.34%, in local wastewaters designed for algae cultivation. Taxonomic genus identification indicated the presence of Calothrix, Pseudomonas, and Clostridium as the most prevalent strains in both local municipal and swine wastewater samples containing algae with an average of 17.37, 12.19, and 7.84%, respectively. Interestingly, swine wastewater without algae displayed the lowest level of Pseudomonas strains < 0.1%. The abundance of some Pseudomonas species in wastewaters containing algae indicates potential coexistence between these strains and algae microenvironment, suggesting further investigations. This finding was particularly relevant for the earlier documented adverse effects of some nosocomial Pseudomonas strains on algae growth and their multidrug resistance potential, requiring the development of targeted bioremediation with regard to the beneficial flora.

http://ift.tt/2i0n3d6

Macroinvertebrate communities in riverine systems of buffer areas of protected wildland, rangeland and city areas: implications for conservation of riverine systems on urbanising watersheds

Abstract

Riverine systems in developing countries continue to be degraded by anthropogenic pressures such as urbanisation. The responses of biota in watersheds surrounding a drainage divide may provide critical information that is required to protect the ecological condition of riverine systems. This study assessed the spatial variation of selected environmental variables together with macroinvertebrate communities in upper reaches of riverine systems across different land use categories of the Bulawayo region. Based on an a priori selection criterion, studied sites were grouped following an urban-wastewater disturbance gradient comprising of (i) heavily polluted city sites, (ii) moderately disturbed rangeland sites and (iii) less disturbed sites of the buffer areas of protected wildland. Most of the studied environmental variables and the macroinvertebrate community assemblages were significantly (ANOVA, p < 0.05) different and degraded within the city areas. In this study, the variance of environmental variables known to be associated with organic pollution like increased nutrients, embeddedness by particulates, salinity, COD, conductivity, turbidity and reduced dissolved oxygen was found to be related with the variation of macroinvertebrate communities across the studied sites. Besides affirming the effectiveness of macroinvertebrate-based bioassessment approaches, the results of our study demonstrate that an aggressive riverine protection policy that prohibits the discharge of poor-quality urban effluents and preservation of the less disturbed riverine systems needs to be part of the larger urban planning and regulatory framework in urbanising watersheds.

http://ift.tt/2gxJOEZ

Relay cropping of wheat ( Triticum aestivum L.) in cotton ( Gossypium hirsutum L.) improves the profitability of cotton-wheat cropping system in Punjab, Pakistan

Abstract

Delayed sowing of wheat (Triticum aestivum L.) in cotton-based system reduces the productivity and profitability of the cotton-wheat cropping system. In this scenario, relay cropping of wheat in standing cotton might be a viable option to ensure the timely wheat sowing with simultaneous improvement in wheat yields and system profitability. This 2-year study (2012–2013 and 2013–2014) aimed to evaluate the influence of sowing dates and relay cropping combined with different management techniques of cotton sticks on the wheat yield, soil physical properties, and the profitability of the cotton-wheat system. The experiment consisted of five treatments viz. (S1) sowing of wheat at the 7th of November by conventional tillage (two disc harrows + one rotavator + two plankings) after the removal of cotton sticks, (S2) sowing of wheat at the 7th of November by conventional tillage (two disc harrows + two plankings) after the incorporation of cotton sticks in the field with a rotavator, (S3) sowing of wheat at the 7th of November as relay crop in standing cotton with broadcast method, (S4) sowing of wheat at the 15th of December by conventional tillage (two disc harrows + one rotavator + two plankings) after the removal of cotton sticks, and (S5) sowing of wheat at the 15th of December by conventional tillage (two disc harrows + two plankings) after the incorporation of cotton sticks in the field with a rotavator. The highest seed cotton yield was observed in the S5 treatment which was statistically similar with the S3 and S4 treatments; seed cotton yield in the S1 and S2 treatments has been the lowest in both years of experimentation. However, the S2 treatment produced substantially higher root length, biological yield, and grain yield of wheat than the other treatments. The lower soil bulk density at 0–10-cm depth was recorded in the S2 treatment which was statistically similar with the S5 treatment during both years of experimentation. The volumetric water contents, net benefit, and benefit-cost ratio were the highest in the S3 treatment during both years of experimentation. Thus, relay cropping of wheat in standing cotton might be a viable option to improve the soil physical environment and profitability of the cotton-wheat cropping system.

http://ift.tt/2i0sQiZ

Assessing watercourse quality: challenges in implementing European and Swiss legal frameworks

Abstract

Hydro-climatic changes and the increasing release of pollutants into rivers by human activities tend to affect the quality of watercourses, to alter aquatic ecosystems and to reduce the amount of useable water. The ecological and chemical states of rivers and their evolution is thus of growing concern. In Europe and Switzerland, water policies are progressively shifting towards a holistic approach of river systems. The European Commission notably established a framework to highlight rivers' ecological deficits and to enhance regional or local water management plans. In Switzerland, a similar framework is currently under development. In this paper, both procedures are compared and implemented in a Swiss catchment dominated by agricultural activities. The aim is to define the challenges that still need to be addressed to assess and sustain river health. The hydromorphological, ecological, and ecotoxicological quality of the river was evaluated. Both frameworks highlighted the fact that no section of the river can currently be classified as being in a good environmental state and that the state deteriorates as tributaries and wastewater discharge flow into the main riverbed. Chemical issues and water quality changes due to hydro-climatic variations and management strategies were also pinpointed. Both frameworks are thus useful tools to survey changes in rivers quality in space and over time. However, challenges remain regarding the appropriate strategies to monitor and analyze chemicals, the definition of target values and conditions, the evaluation and integration of human-induced pressures, and the overall evaluation of the state of a river. The development of integrated indicators or of ecosystem services approaches is considered as a potential solution to explore river health and to define efficient restoration measures by water managers.

http://ift.tt/2gyoWNF

Effect of zero-valent iron and trivalent iron on UASB rapid start-up

Abstract

In order to realize the rapid start-up of upflow anaerobic sludge blanket (UASB) reactor, the iron ion in different valence state was added to UASB. The results indicated that the start-up time of R3 (FeCl₃) was 48 h faster than that of R2 (zero-valent iron (ZVI)). It was because the FeCl₃ could rapidly promote granulation of sludge as a flocculant. However, ZVI released Fe²⁺ through corrosion slowly, and then the Fe²⁺ increased start-up speed by enhancing enzyme activity and enriching methanogens. In addition, the ZVI and FeCl₃ could promote hydrolysis acidification and strengthen the decomposition of long-chain fatty acids. The detection of iron ions showed that iron ions mainly existed in the sludge. Because the high concentration of Fe²⁺ could inhibit anaerobic bacteria activity, excess Fe³⁺ could be changed into iron hydroxide precipitation to hinder the mass transfer process of anaerobic bacteria under the alkaline condition. The FeCl₃ was suitable to be added at the initial stage of UASB start-up, and the ZVI was more fitted to be used in the middle stage of reactor start-up to improve the redox ability.

http://ift.tt/2i0sN6N

Photocatalytic degradation of organic pollutant aldicarb by non-metal-doped nanotitania: synthesis and characterization

Abstract

The current study focused on pollution control by titania through photocatalytic degradation of aldicarb pesticide in aqueous medium. Titania, which is an efficient photocatalyst, can bring about degradation of aqueous organic pollutants under UV and visible light irradiation. Here, we prepared titania by sol-gel method from titanium tetraisopropoxide and doped non-metals like N and S from sources such as urea and thiourea, respectively. The prepared catalyst was characterized by XRD, UV-Vis.DRS, TEM, XPS, etc. Photocatalytic activity of the catalyst was evaluated from extend of degradation of aldicarb pesticide by measuring its concentration with the help of HPLC. It was found that the modified catalyst showed better photocatalytic degradation than pure titania in visible light.

http://ift.tt/2i0sM2J

Multivariate curve resolution of organic pollution patterns in mangrove forest sediment from Qeshm Island and Khamir Port—Persian Gulf, Iran

Abstract

Straight-chain alkanes (n-alkanes) have been proposed as biomarkers to assess petroleum pollution sources in marine environments. In this work, three sampling sites were selected along Iranian-protected mangrove forests in the Persian Gulf. Sample sites were chosen to represent different compositions and sources of n-alkanes in surface sediments (0–5 cm) from different locations in the Khamir Port, in the middle part of the Gulf, and in the Qeshm Island. Samples were analyzed by gas chromatography-mass spectrometry (GC–MS), and the obtained n-alkanes concentrations were analyzed by principal component analysis (PCA) and multivariate curve resolution alternating least squares (MCR-ALS) to deduce their possible sources and distribution patterns. Results revealed that n-alkanes have a dominant biogenic source in marginal Qeshm Island stations, which changed from biogenic to petrogenic sources in the Khamir Port areas. Sediment samples from the Khamir Port showed the significant presence of oil pollution due to transportation. These samples are being exposed to basic Persian Gulf currents entering from the Hormuz Strait causing oil pollution spread over the entire Gulf area. Sediment samples of the Middle Part stations located between two other sites show a combined condition of the two previous sections, with petrogenic and biogenic contributions. The present study demonstrates that the Hara Protected Area was already contaminated by background oil pollution as a result of continuous oil spills and war conflicts in the Persian Gulf.

Additionally, the MCR-ALS method is shown to be a powerful chemometric tool for the investigation, resolution, identification, and description of pollution patterns distributed over a particular geographical area and environmental compartment. They can be used as well as parameters like unresolved to resolved ratio (U/R), pristane to phytane (Pr/Ph), n-C₁₇/Pr, n-C₁₈/Ph, and unresolved complex mixture (UCM) to assess petroleum pollution sources in the sediments.

http://ift.tt/2gyPkqQ

Corn industrial wastewater (nejayote): a promising substrate in Mexico for methane production in a coupled system (APCR-UASB)

Abstract

In Mexico, the corn tortilla is a food of great economic importance. Corn tortilla production generates about 1500–2000 m³ of wastewater per 600 tons of processed corn. Although this wastewater (also known as nejayote) has a high organic matter content, few studies in Mexico have analyzed its treatment. This study presents fresh data on the potential methane production capacity of nejayote in a two-phase anaerobic digestion system using an Anaerobic-Packed Column Reactor (APCR) to optimize the acidogenic phase and an up-flow anaerobic sludge blanket (UASB) reactor to enhance the methanogenic process. Results indicate that day 8 was ideal to couple the APCR to the UASB reactor. This allowed for a 19-day treatment that yielded 96% COD removal and generated a biogas containing 84% methane. The methane yield was 282 L kg⁻¹ of COD_removed. Thus, two-phase anaerobic digestion is an efficient process to treat nejayote; furthermore, this study demonstrated the possibility of using an industrial application by coupling the APCR to the UASB reactor system, in order to assess its feasibility for biomethane generation as a sustainable bioenergy source.

http://ift.tt/2i0sJnz

Occurrence of multi-class surfactants in urban wastewater: contribution of a healthcare facility to the pollution transported into the sewerage system

Abstract

Healthcare facility discharges, by their nature, are often considered as non-domestic effluent, which can provide significant pollution comparatively to other domestic sources. In this context, a total of 12 monthly sampling campaigns were collected from a healthcare facility as well as the output of a sewerage system of Site Pilote de Bellecombe (SIPIBEL) observatory. This study focuses more specifically on 12 surfactants and biocides: four anionics, four cationic, two non-ionic, one zwitterionic, and one dispersive agent, among the most commonly used commercial surfactants. Particular attention was also provided to routine wastewater quality parameters. Both effluents were heavily contaminated by most anionic surfactants; they displayed median concentrations up to 1 to 2 mg/L for linear alkylbenzene sulfonates and between 10 and 100 μg/L for other sodium sulfate congeners (lauryl and laureth). Overall, for the majority of surfactants, the healthcare facility contribution to the total flux reaching the wastewater treatment plant ranges between 5 and 9%.

http://ift.tt/2gzT9MD

Environmental impact assessment of municipal solid waste management options using life cycle assessment: a case study

Abstract

The goal of this study is to use life cycle assessment (LCA) tool to assess possible environmental impacts of different municipal solid waste management (MSWM) scenarios on various impact categories for the study area Dhanbad City, India. The scenarios included in the present study are collection and transportation (denoted as S1); baseline scenario consisting of recycling, open burning, open dumping, and finally unsanitary landfilling without energy recovery (denoted by S2); composting and landfilling (denoted by S3); and recycling and composting followed by landfilling of inert waste without energy recovery (denoted by S4). One ton of municipal solid waste (MSW) was selected as the functional unit. The primary data were collected through sampling, surveys, and literatures. Background data were obtained from Eco-invent data of SimaPro 8.1 libraries. The scenarios were compared using the CML 2 baseline 2000 method, and the results indicated that the scenario S1 had the highest impact on marine aquatic ecotoxicity (1.86E + 04 kg 1,4-DB eq.) and abiotic depletion (2.09E + 02 kg Sb eq.). S2 had the highest impact on global warming potential (9.42E + 03 kg CO₂ eq.), acidification (1.15E + 01 kg SO₂ eq.), eutrophication (2.63E + 00 kg PO₄³⁻ eq.), photochemical oxidation (2.12E + 00 kg C₂H₄ eq.), and human toxicity (2.25E + 01 kg 1,4-DB eq.). However, S3 had the highest impact on abiotic depletion (fossil fuels) (2.71E + 02 MJ), fresh water aquatic ecotoxicity (6.54E + 00 kg 1,4-DB eq.), terrestrial ecotoxicity (3.36E − 02 kg 1,4-DB eq.), and ozone layer depletion (2.73E − 06 kg CFC-11 eq.). But S4 did not have the highest impact on any of the environmental impact categories due to recycling of packaging waste and landfilling of inert waste. Landfilling without energy recovery of mixed solid waste was found as the worst disposal alternative. The scenario S4 was found as the most environmentally suitable technology for the study area and recommended that S4 should be considered for strategic planning of MSWM for the study area.

http://ift.tt/2i0sHfr

Purification of Hg 0 from flue gas by wet oxidation method and its mechanism: a review

Abstract

The vast majority of Hg²⁺ can be removed while elemental mercury (Hg⁰) can hardly be removed due to its characteristic of high volatility and insolubility in water. Till now, how to oxidize Hg⁰ to Hg²⁺ is the key for the purification of Hg⁰, especially when there are others pollutants, such as HCl, SO₂, and NOx. In this review, the method and mechanism of Hg⁰ purification from flue gas by H₂O₂, KMnO₄, NaClO₂, and O₃ are reviewed comprehensively. It is concluded that the oxidation of Hg⁰ mainly depends on the electronic supply efficiency from the solution. The Fenton reagent, composed of H₂O₂ and metal cations, is superior to O₃ and the solution of KMnO₄ and NaClO₂. Moreover, HCl, SO₂, and NOx in the flue gas can influence the oxidation and purification mechanism of Hg⁰. It is found that HCl in flue gas had obvious auxo-action on the oxidation of mercury, and SO₂ and NOx have different effects on the oxidation of Hg⁰ with the change of compositions and concentration of pollutants in the flue gas. In general, SO₂ and NOx can slightly promote the oxidation of Hg⁰ due to the synergistic effect.

http://ift.tt/2gxtS5z

Existing forms and changes of nitrogen inside of horizontal subsurface constructed wetlands

Abstract

Horizontal zeolite subsurface constructed wetland system (HZCWs) and horizontal limestone subsurface constructed wetland system (HLCWs) were applied to the removal of nitrogen in lightly polluted wastewater, and the existing forms, changes, and removal mechanism of nitrogen in the constructed wetlands were analyzed. The results indicated that compared with HLCWs, HZCWs exhibited better nitrogen removal effect, and the maximum removal rates of ammonia nitrogen and total nitrogen could reach 96.97 ± 5.29 and 93.12 ± 3.35%, respectively. Besides, analysis of the removal effect on nitrogen in different existing forms on different substrate heights in the constructed wetlands showed that variation of nitrogen removal efficiency had certain regularities, which were related to the interior construction features of the wetland systems, and agreed with the regularities in the changes of the influential factors such as DO inside of the wetlands. In addition, degradation mechanism of pollutions was also analyzed, and the results indicated that the quantity of microorganisms and enzymes, including FDA, catalase, and urease, on the surface of the substrates had significant influence on the removal regularities and effects of the major pollutions in constructed wetlands.

http://ift.tt/2i0sDwd

Heavy metal and nutrient uptake in plants colonizing post-flotation copper tailings

Abstract

Copper ore mining and processing release hazardous post-flotation wastes that are difficult for remediation. The studied tailings were extremely rich in Cu (1800 mg kg⁻¹) and contaminated with Co and Mn, and contained very little available forms of P, Fe, and Zn. The plants growing in tailings were distinctly enriched in Cu, Cd, Co, Ni, and Pb, and the concentration of copper achived the critical toxicity level in shoots of Cerastium arvense and Polygonum aviculare. The redundancy analysis demonstrated significant relationship between the concentration of available forms of studied elements in substrate and the chemical composition of plant shoots. Results of the principal component analysis enabled to distinguish groups of plants which significantly differed in the pattern of element accumulation. The grass species Agrostis stolonifera and Calamagrostis epigejos growing in the tailings accumulated significantly lower amounts of Cu, but they also had the lowest levels of P, Fe, and Zn in comparison to dicotyledonous. A. stolonifera occurred to be the most suitable species for phytostabilization of the tailings with regard to its low shoot Cu content and more efficient acquisition of limiting nutrients in relation to C. epigejos. The amendments improving texture, phosphorus fertilization, and the introduction of native leguminous species were recommended for application in the phytoremediation process of the tailings.

http://ift.tt/2gzT9w7

The impact of foreign direct investment on CO 2 emissions in Turkey: new evidence from cointegration and bootstrap causality analysis

Abstract

Pollution haven hypothesis (PHH), which is defined as foreign direct investment inducing a raising impact on the pollution level in the hosting country, is lately a subject of discussion in the field of economics. This study, within the scope of related discussion, aims to look into the potential impact of foreign direct investments on CO₂ emission in Turkey in 1974–2013 period using environmental Kuznets curve (EKC) model. For this purpose, Maki (Econ Model 29(5):2011–2015, 2012) structural break cointegration test, Stock and Watson (Econometrica 61:783–820, 1993) dynamic ordinary least square estimator (DOLS), and Hacker and Hatemi-J (J Econ Stud 39(2):144–160, 2012) bootstrap test for causality method are used. Research results indicate the existence of a long-term balance relationship between FDI, economic growth, energy usage, and CO₂ emission. As per this relationship, in Turkey, (1) the potential impact of FDI on CO₂ emission is positive. This result shows that PHH is valid in Turkey. (2) Moreover, this is not a one-way relationship; the changes in CO₂ emission also affect FDI entries. (3) The results also provide evidence for the existence of the EKC hypothesis in Turkey. Within the frame of related findings, the study concludes several polities and presents various suggestions.

http://ift.tt/2i0qiRN

Prevalence of Ideal Cardiovascular Health and Its Association with Cognitive Function in Older Adults: The Chilean National Health Survey (2009–2010)

Rejuvenation Research , Vol. 0, No. 0.


http://ift.tt/2z2lSoB

Response of Human Fetal Liver Progenitor Cell Types to Temperature and pH Stresses In Vitro

Rejuvenation Research , Vol. 0, No. 0.


http://ift.tt/2iudKpM

Improving Surgical Safety and Nontechnical Skills in Variable-Resource Contexts: A Novel Educational Curriculum

Publication date: Available online 23 October 2017
Source:Journal of Surgical Education
Author(s): Yihan Lin, John W. Scott, Sojung Yi, Kathryn K. Taylor, Georges Ntakiyiruta, Faustin Ntirenganya, Paulin Banguti, Steven Yule, Robert Riviello
ObjectiveA substantial proportion of adverse intraoperative events are attributed to failures in nontechnical skills. To strengthen these skills and improve surgical safety, the Non-Technical Skills for Surgeons (NOTSS) taxonomy was developed as a common framework. The NOTSS taxonomy was adapted for low- and middle-income countries, where variable resources pose a significant challenge to safe surgery. The NOTSS for variable-resource contexts (VRC) curriculum was developed and implemented in Rwanda, with the aim of enhancing knowledge and attitudes about nontechnical skills and promoting surgical safety.DesignThe NOTSS-VRC curriculum was developed through a rigorous process of integrating contextually appropriate values. It was implemented as a 1-day training course for surgical and anesthesia postgraduate trainees. The curriculum comprises lectures, videos, and group discussions. A pretraining and posttraining questionnaire was administered to compare knowledge and attitudes regarding nontechnical skills, and their potential to improve surgical safety.SettingThe setting of this study was in the tertiary teaching hospital of Kigali, Rwanda.ParticipantsParticipants were residents of the University of Kigali. A total of 55 residents participated from general surgery (31.4%), obstetrics (25.5%), anesthesia (17.6%), and other surgical specialties (25.5%).ResultsIn a paired analysis, understanding of NOTSS improved significantly (55.6% precourse, 80.9% postcourse, p<0.01). All residents reported that the course would improve their ability to provide safer patient care, and 97.4% believed developing nontechnical skills would improve patient outcomes.ConclusionsNontechnical skills must be highlighted in surgical training in low- and middle-income countries. The NOTSS-VRC curriculum can be implemented without additional technology or significant financial cost. Its deliberate design for resource-constrained settings allows it to be used both as an educational course and a quality improvement strategy. Our research demonstrates it is feasible to improve knowledge and attitudes about NOTSS through a 1-day course, and represents a novel approach to improving global surgical safety.



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Erratum to: Phase 1 study of darolutamide (ODM-201), a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer

http://ift.tt/2xhIvAL

Tribute to Professor Dr. Abdel Moniem Tewfik Hussein

Publication date: September 2017
Source:Arab Journal of Gastroenterology, Volume 18, Issue 3
Author(s): Sherif Mohamed Abdel Fattah




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Editorial Board

Publication date: September 2017
Source:Arab Journal of Gastroenterology, Volume 18, Issue 3





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Competitive Sport Participation Among Athletes With Heart Disease: A Call for a Paradigm Shift in Decision Making.

Author: Baggish, Aaron L. MD; Ackerman, Michael J. MD, PhD; Lampert, Rachel MD

Page: 1569-1571

http://ift.tt/2yIaUkY

Potential Cardiovascular and Total Mortality Benefits of Air Pollution Control in Urban China.

Author: Huang, Chen PhD; Moran, Andrew E. MD, MPH; Coxson, Pamela G. PhD; Yang, Xueli PhD; Liu, Fangchao PhD; Cao, Jie MD; Chen, Kai PhD; Wang, Miao MD; He, Jiang MD, PhD; Goldman, Lee MD; Zhao, Dong MD, PhD; Kinney, Patrick L. ScD; Gu, Dongfeng MD, PhD

Page: 1575-1584

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Divining the Future of Air Pollution in China: Huge Gains in Health Can Be Achieved, but Much Work Remains.

Author: Bell, Griffith A. PhD, MPH; Brauer, Michael ScD

Page: 1585-1587

http://ift.tt/2yLQjhP

The Fluid Mechanics of Transcatheter Heart Valve Leaflet Thrombosis in the Neosinus.

Author: Midha, Prem A. PhD; Raghav, Vrishank PhD; Sharma, Rahul MD; Condado, Jose F. MD, MS; Okafor, Ikechukwu U. PhD; Rami, Tanya MS, MBA; Kumar, Gautam MD; Thourani, Vinod H. MD; Jilaihawi, Hasan MD; Babaliaros, Vasilis MD; Makkar, Raj R. MD; Yoganathan, Ajit P. PhD

Page: 1598-1609

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Anatomy and Flow Characteristics of Neosinus: Important Consideration for Thrombosis of Transcatheter Aortic Valves.

Author: Kapadia, Samir MD; Tuzcu, E. Murat MD; Svensson, Lars G. MD, PhD

Page: 1610-1612

http://ift.tt/2yIaSJS

High-Resolution Chromatin Mapping in Heart Failure: Some Answers, but More Questions.

Author: Mann, Douglas L. MD

Page: 1626-1628

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Circular Noncoding RNA HIPK3 Mediates Retinal Vascular Dysfunction in Diabetes Mellitus.

Author: Shan, Kun PhD *; Liu, Chang MS *; Liu, Bai-Hui PhD; Chen, Xue PhD; Dong, Rui PhD; Liu, Xin PhD; Zhang, Yang-Yang PhD; Liu, Ban PhD; Zhang, Shu-Jie PhD; Wang, Jia-Jian MD; Zhang, Sheng-Hai PhD; Wu, Ji-Hong PhD; Zhao, Chen MD, PhD; Yan, Biao PhD

Page: 1629-1642

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Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials.

Author: Lytvyn, Yuliya PhD *; Bjornstad, Petter MD *; Udell, Jacob A. MD, MPH; Lovshin, Julie A. MD, PhD; Cherney, David Z.I. MD, PhD

Page: 1643-1658

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ESC Congress 2017 in Barcelona: Where the World of Cardiology Came Together.

Author: Bax, Jeroen J. MD, PhD; Achenbach, Stephan MD

Page: 1659-1661

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Dextrocardia: Why Significant Left-Axis Deviation?.

Author: Li, Yuhong PhD; Liu, Renguang PhD; Zhang, Xianglin MD

Page: 1662-1664

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Population Burden of Sudden Death Associated With Hypertrophic Cardiomyopathy.

Author: Aro, Aapo L. MD, PhD; Nair, Sandeep G. MD; Reinier, Kyndaron MPH, PhD; Jayaraman, Reshmy MD; Stecker, Eric C. MD, MPH; Uy-Evanado, Audrey MD; Rusinaru, Carmen MD, PhD; Jui, Jonathan MD, MPH; Chugh, Sumeet S. MD

Page: 1665-1667

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Letter by Koh Regarding Article, "Dipeptidyl Peptidase-4 Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular Interstitial Cells".

Author: Koh, Kwang Kon MD, PhD

Page: 1668-1669

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Letter by Bellien and Kamel Regarding Article, "Dipeptidyl Peptidase-4 Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular Interstitial Cells".

Author: Bellien, Jeremy PharmD, PhD; Kamel, Said PharmD, PhD

Page: 1670-1671

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Response by Choi et al to Letters Regarding Article, "Dipeptidyl Peptidase-4 Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular Interstitial Cells".

Author: Choi, Bongkun PhD; Lee, Sahmin MD, PhD; Chang, Eun-Ju PhD; Song, Jae-Kwan MD, PhD

Page: 1672-1673

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Differential protein-DNA contacts for activation and repression by ArgP, a LysR-type (LTTR) transcriptional regulator in Escherichia coli

Publication date: Available online 23 October 2017
Source:Microbiological Research
Author(s): Phu Nguyen Le Minh, Cristina Velázquez Ruiz, Steven Vandermeeren, Pamella Abwoyo, Indra Bervoets, Daniel Charlier
ArgP is a LysR-type transcriptional regulator (LTTR) that operates with two effector molecules, lysine and arginine, to differentially regulate gene expression. Effector-free ArgP stimulates transcription of all investigated regulon members, except argO, whereas lysine abolishes this effect. Activation of argO, encoding an exporter for arginine and canavanine, is strictly dependent on arginine-bound ArgP. Lysine counteracts this effect and even though lysine-bound ArgP stimulates RNA polymerase recruitment at the argO promoter, the complex is non-productive. It is presently unclear what distinguishes argO from other ArgP targets and how binding of arginine and lysine translates in antagonistic effects on promoter activity. Here we generate high resolution contact maps of effector-free and effector-bound ArgP-DNA interactions and identify the sequence 5′-CTTAT as the consensus recognition motif for ArgP binding. argO is the only operator at which ArgP binding overlaps the −35 promoter element and binding of arginine results in a repositioning of the promoter proximal bound ArgP-arg subunits. This effect was mimicked by the generation of a 10bp insertion mutant (ins-10) in the argO operator that renders its activation by ArgP arginine-independent. ArgP-induced DNA bending of the argO operator by approximately 60° was found to be effector independent. An ArgP:DNA binding stoichiometry of 4:1 indicates binding of four ArgP subunits even to DNA constructs that are truncated for one binding subsite (ΔABS). These results provide insight into the molecular mechanisms of ArgP-mediated regulation and a molecular explanation for the unique arginine-dependence of argO activation that distinguishes this particular ArgP target from all others.



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Solid pseudopapillary tumor of the pancreas: clinical features and imaging findings

Publication date: March–April 2018
Source:Clinical Imaging, Volume 48
Author(s): Dong-Li Li, Hong-Sheng Li, Yi-Kai Xu, Quan-Shi Wang, Rui-Ying Chen, Fang Zhou
This study aimed to report clinical features and CT, MRI, PET/CT findings of solid pseudopapillary tumor (SPT) of the pancreas. Thirty-four patients with pathologically proven SPT were retrospectively reviewed. Most patients were asymptomatic. SPTs in male patients mainly appeared as solid and near solid tumors. Mixed tumors and cystic tumors had larger size than solid and near solid tumors. Solid tumors and solid part of mixed tumors were T2 hyperintense and T1 hypointense and had progressive enhancement. Four tumors (80%) showed markedly even or uneven ¹⁸F-FDG uptake. These characteristic features can help differentiate SPT from other pancreatic neoplasms.



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The influence of surface angle inclination on muscle activity during Pilates based exercises

Publication date: Available online 23 October 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Asia Yates, Ayla Donlin, George Beneck, Evan Schick




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Bipedicled conchal bowl composite sling flap for reconstruction of the upper third of the ear

A 70-year-old male underwent Mohs micrographic surgery to remove an advanced squamous cell carcinoma from his right ear. After extirpation of the tumor resulted in amputation of the superior third of the auricle, the patient worried about his appearance and ability to wear sensory aids.

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VideoEndocrinology™ High-Impact Videos

VideoEndocrinology™
The Official Journal of: American Thyroid Association

FREE ACCESS through November 30, 2017

Watch now:

Transoral Endoscopic Thyroidectomy Vestibular Approach
Angkoon Anuwong, Thanyawat Sasanakietkul, Pornpeera Jitpratoom 

Transoral Endoscopic Thyroidectomy Vestibular Approach
Thanyawat Sasanakietkul, Tobias Carling 

Transoral Endoscopic Parathyroid Cyst Removal
Jonathon O. Russell, Mai G. Al Khadem, and Ralph P. Tufano 

Transoral Robotic Thyroidectomy
Jeremy D. Richmon, Ralph P. Tufano, Jon Russell, Andrew Day, Hamad M. Chaudhary, Salem I. Noureldine 

Transoral Endoscopic Total Parathyroidectomy in Renal Hyperparathyroidism Patient
Thanyawat Sasanakietkul, Wirada Wandee, Pornpeera Jitpratoom, Angkoon Anuwong 

Transoral Excision of Nodal Metastatic Papillary Thyroid Carcinoma
William M. Dougherty, Mark J. Jameson, David C. Shonka Jr. 

The post VideoEndocrinology™ High-Impact Videos appeared first on American Thyroid Association.

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Editors, contents and cover information

Publication date: November 2017
Source:Trends in Biochemical Sciences, Volume 42, Issue 11





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Prediction of sub-surface 37Ar concentrations at locations in the Northwestern United States

Publication date: January 2018
Source:Journal of Environmental Radioactivity, Volume 181
Author(s): Bradley G. Fritz, Craig E. Aalseth, Henning O. Back, James C. Hayes, Paul H. Humble, Pavlo Ivanusa, Emily K. Mace
The Comprehensive Nuclear-Test-Ban Treaty, which is intended to prevent nuclear weapon test explosions and any other nuclear explosions, includes a verification regime, which provides monitoring to identify potential nuclear explosions. The presence of elevated ³⁷Ar is one way to identify subsurface nuclear explosive testing. However, the naturally occurring formation of ³⁷Ar in the subsurface adds a complicating factor. Prediction of the naturally occurring concentration of ³⁷Ar can help to determine if a measured ³⁷Ar concentration is elevated relative to background. The naturally occurring ³⁷Ar background concentration has been shown to vary between less than 1 mBq/m³ to greater than 100 mBq/m³ (Riedmann and Purtschert, 2011). The purpose of this work was to enhance the understanding of the naturally occurring background concentrations of ³⁷Ar, allowing for better interpretation of results. To that end, we present and evaluate a computationally efficient model for predicting the average concentration of ³⁷Ar at any depth under transient barometric pressures. Further, measurements of ³⁷Ar concentrations in samples collected at multiple locations are provided as validation of the concentration prediction model. The model is shown to compare favorably with concentrations of ³⁷Ar measured at multiple locations in the Northwestern United States.



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PD-1 blockade in advanced NSCLC: a focus on pembrolizumab

Publication date: Available online 23 October 2017
Source:Cancer Treatment Reviews
Author(s): Solange Peters, Keith M Kerr, Rolf Stahel
Non–small cell lung cancer (NSCLC) is one of the most prevalent cancers and is responsible for a large proportion of all cancer-related deaths. Current treatment options are inadequate, reflecting a substantial unmet clinical need. Increasing knowledge regarding the mechanisms and genetic aberrations underlying tumor development and growth has heralded a new era of therapy in oncology, moving away from indiscriminate cytotoxic chemotherapy toward more finely focused, targeted medicine. The development of small-molecule drugs and monoclonal antibodies directed toward specific components of dysfunctional molecular or immune pathways, and mutated genes specific to particular cancer types, is leading the field to more personalized and less toxic treatment options, many of which have demonstrated greater efficacy and survival benefits than their chemotherapeutic counterparts. Particularly successful examples are agents that interfere with the programmed death 1 receptor (PD-1) pathway, which many tumors can hijack to avoid immune surveillance and editing. Pembrolizumab, a monoclonal antibody directed at PD-1 that blocks the engagement between PD-1 and its ligands, has been explored as a treatment for solid tumors, and demonstrated survival benefits in several studies. The use of PD-1 inhibitors such as nivolumab and pembrolizumab in advanced cancers is widespread, and pembrolizumab has been available in more than 60 countries for at least one of the following: advanced melanoma, PD-L1–expressing NSCLC, head and neck squamous cell carcinoma, and adult and pediatric patients with refractory classical Hodgkin's lymphoma. This work provides a brief overview of the role of pembrolizumab in the treatment of advanced (recurrent/metastatic) NSCLC.



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Repair of a Large Dorsal Hand Defect With Exposed Tendons.

No abstract available

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Impact of National Comprehensive Cancer Network Guidelines on Case Selection and Outcomes for Sentinel Lymph Node Biopsy in Thin Melanoma.

BACKGROUND: In 2010, the National Comprehensive Cancer Network (NCCN) recommended sentinel lymph node biopsy (SLNB) for thin melanomas =1. In 2016, the criteria were changed to Breslow depth >0.75 mm and MR >=1. OBJECTIVE: To compare the impact of 2010 and 2016 NCCN guidelines on SLNB case selection and thin melanoma outcomes. MATERIALS AND METHODS: Ten-year retrospective cohort of primary thin melanomas at an academic hospital was retroactively stratified for SLNB eligibility using the 2010 and 2016 NCCN guidelines. Nodal recurrence-free survival (NRFS) and disease-free survival (DFS) were compared. RESULTS: Eight hundred two patients with 859 tumors and median follow-up of 79 months were included. Eleven percent fewer tumors qualified for SLNB under 2016 versus 2010 NCCN guidelines (19% vs 8%, p

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Polyalkylimide: A Nonstable Filler Over Time.

BACKGROUND: Polyalkylimide hydrogel is supposed to be a permanent, biocompatible implant. However, years after subcutaneous implantation clinical complications are seen. OBJECTIVE: To increase the understanding of the changes that occur over time in this subdermal implanted filler. MATERIALS AND METHODS: The extruded filler material of 34 patients was evaluated by histologic examination. RESULTS: In most patients who had cosmetic disturbances but no complaints, histology showed no immune cells in or around the filler material. In patients with an acute inflammatory response, giant cell invasion was seen in and around the filler material. Patients with chronic complaints showed a neutrophilic cell influx in the extruded filler. In all patients, degeneration and calcification of the material was noted. The polyalkylimide hydrogel changed over time, both macroscopically and microscopically. As in most of the patients no immune response was seen around the filler material, this may indicate that the material is biocompatible. CONCLUSION: The authors conclude that a dermal filler should not be judged solely on its biocompatible characteristics but also on the degradation process over time in the human body. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Commentary on ATX-101 (Deoxycholic Acid Injection) for Paradoxical Adipose Hyperplasia Secondary to Cryolipolysis.

No abstract available

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Commentary on Improving Sun-Protective Behaviors and Self-Skin Examinations Among African Americans.

No abstract available

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Randomized, Evaluator-Blinded Study Comparing Safety and Effect of Two Hyaluronic Acid Gels for Lips Enhancement.

BACKGROUND: Hyaluronic acid (HA) fillers may differ in terms of gel characteristics and ease of use and it is of interest whether this might affect safety and duration of effect. OBJECTIVE: To compare the long-term safety and effect of 2 HA fillers produced by 2 different technologies for lip enhancement. MATERIALS AND METHODS: Subjects with very thin to moderately thick lips were randomized and treated with HA-RK (N = 31) or HA-JV (N = 29) to improve lip fullness by >= 1 grade on a 5-point scale, using a maximum of 3 mL of product. RESULTS: A smaller volume of HA-RK compared with HA-JV was required to improve lip fullness by >= 1 grade (mean: 1.54 mL vs 1.94 mL, p

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Atypical Melanocytic Proliferations: A Review of the Literature.

BACKGROUND: Ambiguous histopathologic diagnoses represent a challenge for clinicians because of a lack of definitive diagnosis and related uncertainty about management. OBJECTIVE: To review the literature on atypical melanocytic proliferations and detail synonymous terms, epidemiology, diagnostic work-up, histopathology, treatment, and prognosis. METHODS: Databases from PubMed and Web of Science were searched for articles related to atypical melanocytic proliferations. RESULTS: Intraepidermal melanocytic proliferations with features worrisome for possible melanoma in situ (MIS) are generally excised as for MIS. Reported rates of upstaging of such cases to invasive melanoma on review of the excision are very low. Because invasion, lymph node spread, and metastasis can occur in atypical melanocytic lesions with a thick intradermal component, these are often treated as for malignant melanoma. CONCLUSION: Because the diagnosis dictates treatment, it is incumbent to establish a diagnosis as definitive as possible, obtaining second or third opinions and using ancillary studies when appropriate. When the diagnosis remains uncertain, it is difficult to provide guidelines for treatment. Clinical care decisions for patients with an uncertain diagnosis are best done on a case-by-case basis weighing probabilities of adverse outcomes against potential benefits and risks from various treatment options. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Cohesion of Hyaluronic Acid Fillers: Correlation Between Cohesion and Other Physicochemical Properties.

BACKGROUND: There are several published articles on characterization of fillers, describing methods for both chemical and physicochemical characterization. Recently a lot of focus has been on the development of methods for measuring cohesion of hyaluronic acid (HA) fillers. OBJECTIVE: The aim of this study is to investigate and compare the drop-weight method and the correlation between cohesion and other physicochemical properties using a variety of HA fillers. MATERIALS AND METHODS: HA fillers covering several product families and manufacturing techniques were used. The HA fillers also covered a range of HA concentrations from 12 to 24 mg/mL. Cohesion was determined using sensory evaluation and the drop-weight method. Other physicochemical properties evaluated were rheology and the swelling factor. RESULTS: In this study, it was verified that values obtained by the drop-weight method reflect the perceived cohesion very well. The correlation with rheology is affected by the HA concentration in the products. A remarkably good correlation between swelling factor and cohesion was found. CONCLUSION: Cohesion correlates with other physicochemical methods. It could be discussed whether there is a need for a separate cohesion method because other already established physicochemical methods such as rheology and swelling factor can describe the underlying properties that affect cohesion. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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CXCR5+CD8+ T cells could induce the death of tumor cells in HBV-related hepatocellular carcinoma

Publication date: December 2017
Source:International Immunopharmacology, Volume 53
Author(s): Yun Jin, Cuicui Lang, Jianzhong Tang, Jiawei Geng, Haihan K. Song, Zhiwei Sun, Jinfeng Wang
The follicular CXCR5⁺CD8⁺ T cells have recently emerged as a critical cell type in mediating peripheral tolerance as well as antiviral immune responses during chronic infections. In this study, we investigated the function of CXCR5⁺CD8⁺ T cells in HBV-related hepatocellular carcinoma patients. Compared to CXCR5⁻CD8⁺ T cells, CXCR5⁺CD8⁺ T cells presented elevated PD-1 expression but reduced Tim-3 and CTLA-4 expression. Upon anti-CD3/CD28 stimulation, CXCR5⁺CD8⁺ T cells demonstrated higher proliferation potency than CXCR5⁻CD8⁺ T cells, especially after PD-1 blockade. CXCR5⁺CD8⁺ T cells also demonstrated significantly higher granzyme B synthesis and release, as well as higher level of degranulation. Tumor cells were more readily eliminated by CXCR5⁺CD8⁺ T cells than by CXCR5⁻CD8⁺ T cells. Interestingly, we found that B cells were more resistant to CXCR5⁺CD8⁺ T cell-mediated killing than tumor cells, possibly through IL-10-mediated protection. In addition, the CXCR5⁺CD8⁺ T cell-mediated cytotoxic effects on tumor cells could be significantly enhanced by PD-L1 blockade. Together, we presented that in patients with in HBV-related hepatocellular carcinoma, CXCR5⁺CD8⁺ T cells could mediate tumor cell death more potently than the CXCR5⁻CD8⁺ T cells in vitro while the autologous B cells were protected.



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Genipin inhibits allergic responses in ovalbumin-induced asthmatic mice

Publication date: December 2017
Source:International Immunopharmacology, Volume 53
Author(s): Je-Won Ko, Na-Rae Shin, Sung-Hyeuk Park, Young-Kwon Cho, Jong-Choon Kim, Chang-Seob Seo, In-Sik Shin
Genipin is a natural compound isolated from the fruit of Gardenia jasminoides with various pharmacological effects. In this study, we investigated whether genipin effectively alleviates allergic responses in a murine model of ovalbumin (OVA)-induced asthma. The mice were administered an intraperitoneal injection of OVA on day 0 and 14 to boost the immune response; genipin was then administered from day 18 to 23 by oral gavage. On days 21 to 23, mice were OVA-challenged using am ultrasonic nebulizer, and airway hyperresponsiveness (AHR) was determined on day 24 by plethysmography. Genipin significantly reduced the inflammatory cell count in bronchoalveolar lavage fluids (BALF) and AHR, which were accompanied by lower interleukin-5 (IL-5), IL-13 and OVA-specific immunoglobulin (Ig) E levels in the BALF or serum from OVA-induced asthmatic mice. In histology, genipin significantly decreased airway inflammation and mucus hypersecretion in OVA-induced asthmatic mice. Additionally, genipin inhibited OVA-induced increases in the expression of inducible nitric oxide synthase and cyclooxygenase-2 proteins. Further, genipin reduced the activity and protein levels of matrix metalloproteinase-9 in lung tissue from OVA induced asthmatic mice. Overall, genipin effectively alleviated the asthmatic inflammatory response in an OVA-induced asthmatic model. Therefore, our results suggest that genipin has therapeutic potential for treating asthma.

Graphical abstract

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Docosahexaenoic acid attenuates carbon tetrachloride-induced hepatic fibrosis in rats

Publication date: December 2017
Source:International Immunopharmacology, Volume 53
Author(s): Jianlin He, Kaikai Bai, Bihong Hong, Feng Zhang, Shizhong Zheng
Fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has been reported to exert beneficial health effects, including hepatoprotection. However, the effect of DHA alone has not been well studied, and the mechanism is not fully understood. In the present study, we reported the protective effect of DHA on carbon tetrachloride (CCl4) induced hepatic fibrosis. Compared with the control group, the CCl4 group showed hepatic damage as evidenced by histological changes and elevation in serum transaminase activity, fibrosis, inflammation and oxidative stress levels. These pathophysiological changes were attenuated by chronic DHA supplementation. The anti-fibrotic effect of DHA was accompanied by reductions in gene and protein expression of α-smooth muscle actin (α-SMA), fibronectin, and collagen in the liver tissue. DHA also attenuated CCl4-induced elevation of lipid peroxidation (LPO) and decrease of glutathione (GSH)/oxidized GSH (GSSG) ratio. The upregulated inflammatory cytokines tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-6 by CCl4 were also ameliorated by DHA. Peroxisome proliferator-activated receptor (PPAR)-γ upregulation and type I and II receptors for transforming growth factor (TGF)-β (Tβ-RI and Tβ-RII) and platelet-derived growth factor (PDGF)-β receptor (PDGF-βR) downregulation on both mRNA and protein levels were observed by DHA treatment compared to CCl4 group. Moreover, in vitro study showed that DHA inhibited HSC activation, being associated with elevating PPARγ level and reducing the phosphorylation levels of Smad2/3 and ERKs, which are downstream intermediates of TGFβ and PDGF receptors, respectively. Taken together, the hepatoprotective, anti-inflammatory and anti-fibrotic effects of DHA appeared to be multifactorial. Further, one of the mechanisms of the anti-fibrotic effect of chronic DHA supplementation is probably through PPARγ signaling to interrupt TGFβ/Smad and PDGF/ERK pathways in HSCs.



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Inhaled glucocorticoid treatment prevents the response of CD8+ T cells in a mouse model of allergic asthma and causes their depletion outside the respiratory system

Publication date: December 2017
Source:International Immunopharmacology, Volume 53
Author(s): Monika Zuśka-Prot, Tomasz Maślanka
The principal objective of this research has been to determine the safety of inhaled glucocorticoids (GCs) in respect of their effect on CD8⁺ T cells within respiratory and extra-respiratory tissues, and to compare it with systemic GC treatment. Another purpose has been to identify whether inhaled and systemic GCs affect the CD8⁺ T cell response in the mediastinal lymph nodes (MLNs) and lungs in a mouse model of ovalbumin (OVA)-induced asthma. Ciclesonide and methylprednisolone were used as a model for inhaled and systemic GCs, respectively. The CD8⁺ T cell response was observed in untreated OVA-immunized mice, manifesting itself by the proliferation of these cells and their recruitment into the lower respiratory tract. Inhaled and systemic GC treatment fully prevented this response. This suggests that one of the elements contributing to the anti-asthmatic efficacy of inhaled and systemic GCs could be the inhibition of the effector CD8⁺ T cell response which accompanies the disease. The anti-asthmatic effect of GCs was rather not mediated through the generation or/and increased recruitment of Foxp3⁺CD25⁺CD8⁺ regulatory T cells into the MLNs and lungs. Inhaled and systemic GCs produced comparable depletions of normal CD8⁺ T cells in the MLNs, the head and neck lymph nodes and in peripheral blood, and this effect, at least to some extent, resulted from the proapoptotic action of GCs towards these cells. These results suggest that inhaled GC therapy might not be safer at all than treatment with systemic GCs in respect of the undesirable effects on CD8⁺ T cells residing within and outside the respiratory tract.



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Quercetin protects mouse liver against triptolide-induced hepatic injury by restoring Th17/Treg balance through Tim-3 and TLR4-MyD88-NF-κB pathway

Publication date: December 2017
Source:International Immunopharmacology, Volume 53
Author(s): Cai-Bing Wei, Kun Tao, Rong Jiang, Lian-Di Zhou, Qi-Hui Zhang, Chun-Su Yuan
Triptolide (TP) is a diterpene triepoxide with various biological activities, but its clinical applications have been limited by potential hepatotoxicity, which can be attributed to T helper 17 (Th17)/T regulatory (Treg) cell imbalance. Quercetin (QE), a natural flavonoid, has been reported to have many benefits and medicinal properties, including hepatoprotective activity against TP-induced liver injury. However, the hepatoprotection mechanisms have not been clarified. The present study was designed to explore the protective effect and the mechanism of QE against TP-induced liver injury. Treatment with QE (20, 50 and 80mg/kg) prior to TP administration restored TP-induced alterations in a certain dose range indicating that QE was able to inhibit TP-induced liver injury. One mechanism underlying this effect was the shifting balance in Th17 and Treg cells from Th17 dominance to Treg dominance. Furthermore, QE markedly decreased the expression level of the Th17-related pro-inflammatory cytokines interleukin (IL)-17 and IL-6, as well as the Th17 transcription factor retinoid-related orphan receptor-γt (ROR-γt). TP induced downregulation in the expression of anti-inflammatory cytokine IL-10, but the expression of Treg transcription factor forkhead/winged-helix family transcriptional repressor p3 (FoxP3) was restored by QE. In the process of exploring the possible hepatoprotective mechanisms of QE, we found that QE significantly reduced both protein and mRNA expression of Toll-like receptor 4 (TLR4), which in turn not only inactivated myeloid differentiation primary response gene 88 (MYD88), nuclear factor kappa B (NF-κB) and related inflammatory cytokines IL-6 and IL-17, but also simultaneously increased the levels of T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3). Furthermore, blocking of TLR4 enhanced the effect of QE in regulating the Th17/Treg imbalance. In summary, this report has demonstrated for the first time that the protection afforded by QE against TP-induced liver injury was associated with a shift in the balance of Th17 and Treg cells to Treg dominance, which was regulated by Tim-3 and TLR4-MyD88-NF-κB signaling pathway.

Graphical abstract

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Immunogenicity and protective efficacy of multistage vaccine candidates (Mtb8.4-HspX and HspX-Mtb8.4) against Mycobacterium tuberculosis infection in mice

Publication date: December 2017
Source:International Immunopharmacology, Volume 53
Author(s): Wanbo Liu, Jingjing Li, Hongxia Niu, Xiaofa Lin, Ruiying Li, Yue Wang, Qi Xin, Hongjuan Yu, Yumin Wu, Bingdong Zhu, Jiying Tan
In this study, Mtb8.4 and HspX, which are expressed at proliferating and dormant stages of Mycobacterium tuberculosis (M. tuberculosis), respectively, were chosen to construct two fusion proteins, Mtb8.4-HspX (8.4H) and HspX-Mtb8.4 (H8.4), and we investigated whether the antigen dose and protein sequential order could impact the immunogenicity and protective efficacy of these fusion protein vaccines against M. tuberculosis. C57BL/6 mice were vaccinated with new constructions containing a fusion protein with adjuvant of N, N′-dimethyl-N, N′-dioctadecylammonium bromide (DDA) or a mixed adjuvant composed of DDA, polyribocytidylic acid and gelatin (DPG), and the antigen specific immune responses and protective efficacy against M. tuberculosis H37Rv were evaluated. The results showed that both antigens, Mtb8.4-HspX and HspX-Mtb8.4, could elicit strong human T cell responses. With the existing of DDA adjuvant, HspX-Mtb8.4 induced significantly higher secretion level of IFN-γ and TNF-α in spleen cells than Mtb8.4-HspX (p<0.05). In its protective efficacy study, the isolated bacterial Colony Form Unit (CFU) in H8.4-DPG group was significantly reduced compared to 8.4H–DPG group (p<0.05). Furthermore, with the stimulation of Mtb8.4 in vitro, the secretion of IFN-γ and TNF-α from mice immunized with 20μg of H8.4 exhibited relative higher level than the group immunized by 7μg of H8.4 (p<0.05), whereas, IL-2 secreting showed contrary result. The data suggest that the antigen sequential order and dose selection should be considered when a tuberculosis protein vaccine is to be constructed and its immune strategy is to be planned.



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Pinocembrin attenuates allergic airway inflammation via inhibition of NF-κB pathway in mice

Publication date: December 2017
Source:International Immunopharmacology, Volume 53
Author(s): Xiaoyan Gu, Qian Zhang, Qiang Du, Hong Shen, Zhenghua Zhu
Pinocembrin, one of the primary flavonoids in propolis, possesses many biological activities, including anti-inflammation, anti-oxidation and immunoregulation. This study aimed to evaluate whether pinocembrin could attenuate ovalbumin (OVA)-induced allergic airway inflammation in mice and to explore the possible mechanism. BALB/c mice sensitized and challenged with OVA were administered intraperitoneally with pinocembrin. Airway inflammation and airway hyperresponsiveness were examined. T-helper type (Th) 2 cytokines in bronchoalveolar lavage fluid (BALF) and OVA-specific immunoglobulin E (IgE) in serum were determined. The activation of nuclear factor kappa B (NF-κB) p65 were also measured. Our results showed that pinocembrin resulted in significant inhibition of pathophysiological signs of allergic asthma, including increased pulmonary eosinophilia infiltration, mucus hypersecretion and airway hyperresponsiveness (AHR). Treatment with pinocembrin significantly reduced Th2 cytokines interleukin (IL)-4, IL-5 and IL-13 in BALF, and OVA-specific IgE in serum. Moreover, pinocembrin treatment suppressed phosphorylation of inhibitor-κBα (IκBα) and NF-κB subunit p65 activation in lung tissue of OVA-sensitized mice. These data suggest that pinocembrin may inhibit allergic airway inflammation, and providing potential benefits in the treatment of inflammatory disease.



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Design, isolation and evaluation of the binding efficiency of a DNA aptamer against interleukin 2 receptor alpha, in vitro

Publication date: December 2017
Source:International Immunopharmacology, Volume 53
Author(s): Mahin Shahdordizadeh, Seyed Mohammad Taghdisi, Mojtaba Sankian, Mohammad Ramezani, Khalil Abnous
High levels of CD25, as part of the IL-2 receptor, are expressed on the surface of the activated T lymphocytes and regulatory T cells, indicating that the soluble CD25 (sCD25) could be a clinically valuable tool for treating several diseases. Moreover, progress has been achieved in targeting the IL-2 receptor to treat autoimmune diseases, organ transplantation and certain hematological malignancies. In the current study, generation of an ssDNA aptamer (Apt51) against CD25 is reported. Apt51 bound to CD25 with high affinity (Kd=13.4nM) and specificity. Furthermore, Apt51 was truncated to two shortened variants that almost retained their high affinity for the CD25 protein. Moreover, Apt51 showed good affinity and selectivity for the recognition of CD25 on the cell surface. Importantly, the study showed that Apt51 interfered with the binding of CD25 to its ligand (IL 2) and consequently decreased the IL-2-induced Akt activation.



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Inside front cover

Publication date: November 2017
Source:International Immunopharmacology, Volume 52





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Refractory Giant Cell Arteritis Complicated by Vision Loss From Optic Atrophy and Maculopathy Associated With Pachymeningitis.

Background: We describe a 75-year-old woman who experienced vision loss in her left eye due to biopsy-proven giant cell arteritis (GCA). She subsequently developed pachymeningitis causing refractory headaches and bilateral optic neuropathy and maculopathy. Methods: Case report with literature review. Results: Eighteen months after the initial diagnosis of GCA, imaging studies in our patient demonstrated pachymeningeal enhancement, and meningeal biopsy confirmed lymphoplasmacytic tissue infiltrates with low frequencies of IgG4+ plasma cells. Laboratory investigation revealed the presence of 3 antiretinal antibodies and antimyeloperoxidase antibodies, consistent with autoimmune retinopathy. Treatment with B-cell-depleting anti-CD20 antibodies suppressed meningeal inflammation and prevented further vision loss. Conclusions: This case illustrates that bilateral vision loss and chronic headaches in patients with GCA may result from retina-directed autoimmunity and pachymeningitis. (C) 2017 by North American Neuro-Ophthalmology Society

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Cutaneous Presentation of Mesothelioma With a Sarcomatoid Transformation.

Malignant pleural mesothelioma is a rare neoplasm of mesodermal origin. Cutaneous involvement of malignant pleural mesothelioma is a very rare entity, with only 11 cases reported in the literature. Here, we describe the case of a 75-year-old man with stage IV epithelioid pleural mesothelioma, presenting with a cutaneous eruption 5 months after initial diagnosis, which revealed sarcomatoid features on skin biopsy. Histological analysis of malignancy progression through immunohistochemical staining of the pleural, lymph node, and skin tissue revealed gradual loss of calretinin and gain of desmin, supporting a transformation from epithelioid to sarcomatoid tissue. To our knowledge, this is the first reported case of an epithelioid to sarcomatoid transformation of malignant pleural mesothelioma manifesting in a cutaneous presentation. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Proliferative Melanocytic Nodule on Small Congenital Nevus During Treatment With Etanercept.

No abstract available

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Retraction

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Erratum

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Immediate and Long-term Results of Radiofrequency Ablation for Colorectal Liver Metastases

Background/Aim: Radiofrequency ablation (RFA) of colorectal liver metastases (CRLMs) is a method developed in the last 15 years. It provides an acceptable control of the malignant process with lower risks compared to surgical resection. The aim of the study was to assess immediate and long-term results, including recurrence, survival, morbidity/mortality rates after RFA. Patients and Methods: Sixty-two cases with CRLMs were treated by RFA during open surgery (89 lesions). Patients were followed-up for a minimum of 36 months, with assessment of recurrences and survival rates at 1, 2 and 3 years, using computed tomography (CT) scan, contrast-enhanced ultrasound and tumor markers (carcinoembryonoc antigen, carbohydrate antigen-19.9). Results: Local relapses, recurrences in other areas and survival rates at 1, 2 and 3 years suggest acceptable values comparative with liver resections in the first 2-3 years and demonstrated long-term limitations, despite the use of adjuvant chemotherapy. Major postoperative negative prognostic factors are tumor multicentricity and tumor's dimensions over 5 cm. Conclusion: RFA of CRLMs is a safe procedure with low rates of local relapses and recurrences, as well as acceptable survival rates, in the first 24-36 months post-procedure. It is recommended for patients with no indications for liver resection or having major resection risks.

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Evaluation of Efficacy and Safety of Upfront Weekly Nanoparticle Albumin-bound Paclitaxel for HER2-negative Breast Cancer

Background: Taxanes are among the key drugs for breast cancer treatment. This study aimed to evaluate the efficacy of upfront weekly nanoparticle albumin-bound paclitaxel (Nab-PTX; 100 mg/m²) for human epidermal growth factor 2 (HER2)-negative breast cancer. Patients and Methods: Patients with stage II to IV breast cancer received 12 cycles of weekly 100 mg/m² Nab-PTX as first-line treatment. Preoperative chemotherapy with anthracyclines after Nab-PTX was recommended. Results: From 2012 to 2014, we enrolled 66 patients. The overall response rate after Nab-PTX was 59.1% [95% confidence interval(CI)=47.2% to 71.0%), 63.6% in those with hormone receptor-positive tumors, and 36.4% in those with triple-negative tumors. The pathological complete response rate at surgery was 15% (95% CI=6.1% to 24.4%). Toxicity analysis showed grade 2 peripheral neuropathy in 38 patients (57.6%), grade 2/3 leukocytopenia in 29 (43.9%) and grade 2/3 liver dysfunction in five (7.5%). Conclusion: Weekly neoadjuvant Nab-PTX at 100 mg/m² led to good response rates (59.1%) and was well tolerated.

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Clinical Efficacy of Alectinib in Patients with ALK-Rearranged Non-small Cell Lung Cancer After Ceritinib Failure

Several second-generation inhibitors of anaplastic lymphoma kinase (ALK) have demonstrated potent activity in ALK rearrangement-positive non-small cell lung cancer (NSCLC). Two of these agents, ceritinib, and alectinib, recently received approval for the treatment of ALK-rearranged NSCLC in Japan. The efficacy of treatment with a second-generation ALK inhibitor after failure with a different second-generation ALK inhibitor remains unclear. We present a series of eight patients with ALK-rearranged NSCLC treated with alectinib who experienced disease progression after ceritinib. Both crizotinib and ceritinib were administered to six patients, with four (29%) patients receiving crizotinib followed by ceritinib. Among the eight study patients, two (25%) had partial response, one (12%) stable disease, and five (63%) had progressive disease. The median progression-free survival was 3.6 months (95% confidence interval=0-7.1 months). The results of this study suggest that the second-generation ALK inhibitor alectinib has limited efficacy after initial treatment with the second-generation ALK inhibitor ceritinib.

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Serum Concentration of Erlotinib and its Correlation with Outcome and Toxicity in Patients with Advanced-stage NSCLC

Background: Erlotinib is a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR); it is used in the treatment of advanced non-small cell lung cancer (NSCLC). We focused on the role of serum concentration of erlotinib and its association with outcome and toxicity in patients with advanced NSCLC harbouring the wild-type EGFR gene or squamous histology. Patients and Methods: Clinical data of 122 patients were analyzed. Serum samples were collected within four weeks after the initiation of treatment. Results: There was no significant association of erlotinib concentration with PFS nor OS (p=0.352 and p=0.6393). Significant associations of erlotinib concentration with grade of skin rash and diarrhoea (p<0.0001 and p<0.0001) were found. Skin rash and diarrhoea were significantly associated with PFS (p=0.0338 and p=0.0001) and OS (p=0.0064 and p=0.0353). Conclusion: Erlotinib concentration was not associated with outcome. Erlotinib concentration was associated with occurrence and severity of skin rash and diarrhoea; the outcome was associated with erlotinib toxicity.

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Anti-Epidermal Growth Factor Receptor Antibody Readministration in Chemorefractory Metastatic Colorectal Cancer

Background/Aim: Readministration of anti-epidermal growth factor receptor (EGFR) antibody for metastatic colorectal cancer (mCRC) after disease progression remains to be determined. Patients and Methods: Readministration of anti-EGFR antibody in mCRC patients previously refractory to anti-EGFR antibody was prospectively observed. Results: A total of thirteen patients with a median age of 60-years old and an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, were enrolled. The median number of previous chemotherapies was 3 (range 2-5). Prior anti-EGFR antibody in combination with cytotoxic drugs was administered in 12 patients. Anti-EGFR antibody readministration regimens were cetuximab/panitumumab plus capecitabine/S-1 (seven patients), panitumumab plus FOLFOX (three patients), cetuximab plus irinotecan (two patients), and panitumumab monotherapy (one patient). Seven patients showed stable disease following readministration and six patients showed progressive disease. The median overall survival (OS) following readministration was 228 days and the median PFS was 102 days. Patients with intervals longer than 90 days between anti-EGFR therapies exhibited more favorable survival than those with intervals shorter than 90 days. Switching of anti-EGFR antibody between treatments was observed to contribute survival. Conclusion: Anti-EGFR antibody readministration could show a modest survival benefit in mCRC patients, with the length of therapy interval and switching of antibody being important contributory factors.

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Neoadjuvant Chemotherapy for Patients with Muscle-invasive Urothelial Bladder Cancer Candidates for Curative Surgery: A Prospective Clinical Trial Based on Cisplatin Feasibility

Background: Neoadjuvant chemotherapy demonstrated a survival benefit versus cystectomy alone in muscle-invasive urothelial bladder cancer. Despite this advantage, preoperative chemotherapy is not widely employed. When patients are unfit for cisplatin-based regimen, they are often candidates for immediate surgery. In our study, patients with muscle-invasive bladder cancer were treated with neoadjuvant chemotherapy. The principal objective was the rate of complete pathological response (pCR). Secondary end-points were disease-free survival (DFS), overall survival (OS) and toxicity. Patients and Methods: Patients (n=72) with Eastern Cooperative Oncology Group (ECOG) performance status 0-1, clinical stage cT3-4, and/or N+ muscle-invasive bladder cancer were enrolled. The chemotherapy regimen was established according to the cisplatin feasibility. Thirty patients were treated with cisplatin/gemcitabine (Gem) and 42 with carboplatin/Gem. Results: The rate of pCR was 29.2%, 36% with cisplatin-based treatment and 23.8% with carboplatin (p=0.3574). DFS and OS were longer in pCR patients, while no difference was reported between cisplatin/Gem and Carboplatin/Gem groups. Conclusion: Our results confirm the prognostic value of pCR in neoadjuvant chemotherapy for muscle-invasive bladder cancer. When the patients are not fit for cisplatin, a carboplatin/Gem regimen represents a valid option because of comparable long-term outcome. When cisplatin is not feasible, the exclusion of a preoperative treatment is not justified.

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Bladder Urothelial Carcinoma with Peritoneal Involvement: Benefit of Continuous Maintenance Chemotherapy

Aim: We investigated bladder urothelial carcinoma with peritoneal involvement. Patients and Methods: Inclusion criteria were: pathology-confirmed urothelial carcinoma; peritoneal spread identified on computed tomographic (CT) scans performed initially or after either cystectomy or concomitant chemoradiotherapy (CCRT), and absence of visceral metastases; and chemotherapy administered after peritoneal spread was diagnosed. Results: Forty-seven cases included initial modes of therapy with chemotherapy in 24 patients (51%), cystectomy in 17 (36%), and CCRT in six (13%), only given as a result of under-staging. After local therapy, these patients received a continuous maintenance chemotherapy regimen of 5-fluorouracil, leucovorin, cisplatin, and gemcitabine. The overall response rate was 85%, and the side-effects were mild and tolerated. The median survival time was 28 months. The survival time of cases initially treated only with chemotherapy was not statistically different to that of those with local disease. Conclusion: Bladder urothelial carcinomas with peritoneal involvement can benefit from continuous maintenance chemotherapy.

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Vinflunine in the Treatment of Upper Tract Urothelial Carcinoma - Subgroup Analysis of an Observational Study

Background/Aim: Despite an expected prognostic disadvantage for upper tract versus lower tract metastatic urothelial carcinomas (UTUC/LTUC), only few studies have been conducted to elucidate potential differences in chemotherapy treatment. Patients and Methods: A post-hoc subgroup analysis of a non-interventional study investigating vinflunine after failure of a platinum-based chemotherapy in metastatic/locally advanced UC patients was performed. Results: A total of 18 and 59 out of 77 patients had UTUC and LTUC, respectively. The effectiveness of vinflunine treatment was comparable with an overall response rate of 22.2% and 23.7% respectively and a median progression-free survival of 2.76 months in both groups. Median overall survival was 5.0 months in UTUC compared to 8.2 months in the LTUC group (p=0.478). The safety profile was in accordance with previous vinflunine experiences, with a comparable frequency of adverse events in both groups. Conclusion: Vinflunine can be applied in the 2nd line for UC regardless of the primary tumor localization.

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Survival Outcomes According to TIMP1 and EGFR Expression in Heavily Treated Patients with Advanced Non-small Cell Lung Cancer who Received Biweekly Irinotecan Plus Bevacizumab

Background: Heavily treated patients with non-small cell lung cancer (NSCLC) have few treatment options, while irinotecan and bevacizumab have proven synergistic action in preclinical studies. Patients and Methods: A total of 49 patients with heavily treated NSCLC were enrolled from 2011-2014 and treated with irinotecan and bevacizumab. Treatment response along with mutational status of epidermal growth factor receptor (EGFR), and tissue inhibitor of metalloproteinases-1 (TIMP1) and EGFR expression were evaluated. Progression-free (PFS) and overall (OS) survival were monitored. Results: Median follow-up was 13.2 months. Twenty-three patients had received three or more prior therapy lines. Overall response rate was 32% [95% confidence interval (CI)=22%-39%] and 26% of patients achieved stable disease. Median PFS was 4.4 (95% CI=2.8-8.3) months and median OS 18.0 (95% CI=16.2-30.7) months. Nine patients harboring EGFR mutations had a long-lasting partial response. A shorter OS was found in patients with a higher TIMP1 expression (p=0.006). Conclusion: Irinotecan combined with bevacizumab had favorable antitumor activity in heavily pretreated patients with NSCLC. These results suggest this is a reasonable strategy, particularly for patients with low TIMP1 expression.

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Effect of Adjuvant Gemcitabine Combined with Low-dose 5-Fluorouracil and Cisplatin Chemotherapy for Advanced Biliary Carcinoma

Background/Aim: The aim of this retrospective study was to clarify the effectiveness of chemotherapy with gemcitabine combined with low-dose 5-fluorouracil and cisplatin (GFP) for advanced biliary carcinoma after hepatectomy. Patients and Methods: Sixty-two patients had biliary carcinoma with lymph node metastasis, intrahepatic metastasis or positive surgical margins, including intrahepatic cholangiocarcinoma (IHC, n=25), hilar cholangiocarcinoma (HC, n=14), and gallbladder cancer (GBC, n=23). Twenty-eight patients (IHC; n=9, HC; n=8, GBC; n=11) received adjuvant GFP chemotherapy. Results: We found no significant difference in clinicopathological factors in patients treated with or without adjuvant GFP chemotherapy. Overall, survival in the adjuvant GFP group was significantly better than that in the non-adjuvant GFP group (3-year survival: 61.9% vs. 8.8%, p<0.001), as was relapse-free survival. Conclusion: Adjuvant GFP chemotherapy after hepatectomy may be a promising option for improving surgical outcomes in patients with advanced biliary carcinoma.

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Lactoperoxidase, an Antimicrobial Milk Protein, as a Potential Activator of Carcinogenic Heterocyclic Amines in Breast Cancer

Background: Lactoperoxidase (LPO) is an antimicrobial protein secreted from mammary, salivary and other mucosal glands. It is an important member of heme peroxidase enzymes and the primary peroxidase enzyme present in breast tissues. In addition to the antimicrobial properties, LPO has been shown to be associated with breast cancer etiology. Heterocyclic amines, an important class of environmental and dietary carcinogens, have been increasingly associated with breast cancer etiology. Heterocyclic amines undergo activation in breast tissue as a result of oxidation by LPO. The current study includes three important heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methy-6-phenylimidazo[4,5-b]-pyridine (PhIP), that have carcinogenic activity. Materials and Methods: The structural binding characterization of IQ, MeIQx and PhIP with LPO was done using in silico approaches. Their binding pattern and interactions with LPO amino acid residues were analyzed. Results: The three compounds bound in the distal heme cavity of LPO without replacing the important water molecule required for oxidation of substrate compounds. PhIP displayed lesser binding affinity for LPO in comparison to IQ and MeIQx. The binding mode of heterocyclic amines in distal heme cavity of LPO resembled to that of substrate binding pattern. Conclusion: The three heterocyclic amines are suggested to act as LPO substrate. The undisturbed water molecule present in distal heme cavity of the LPO is expected to facilitate the oxidation and activation of the three heterocyclic amines. These activated compounds may potentially bind with DNA in breast tissues forming DNA adducts and may subsequently lead to breast cancer initiation.

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Batatasin III Inhibits Migration of Human Lung Cancer Cells by Suppressing Epithelial to Mesenchymal Transition and FAK-AKT Signals

Background/Aim: Lung cancer is the leading cause of cancer-related deaths worldwide. Compound Batatasin III isolated from Dendrobium draconis Rchb.f. was tested for the possible anti-cancer activities including anti-proliferative, anti-migration and invasion in human non-small lung cancer H460 cells. Materials and Methods: The effect of Batatasin III on viability and proliferation of H460 cells was investigated by the 3-[4,5-dimethylthiazol-2-yl]-2,5diphenyl tetrazoliumbromide (MTT) assay. Migration and invasion assays were performed. Filopodia formation was determined by phalloidin-rhodamine staining. The hallmark signaling proteins in regulation of epithelial to mesenchymal transition (EMT), proliferation, and migration were determined by western blot analysis. Results: Batatasin III at concentrations lower than 100 μM has no cytotoxic effects. The compound at 25-100 μM exhibited anti-proliferative activity at 48 h after treatment. Regarding cell motility, Batatasin III decreased migration and invasion of cells. Filopodia were found to be significantly reduced in Batatasin III treated cells. These effects correlated with the results from western blot analysis showing that the phosphorylation of focal adhesion kinase on Try397 (p-FAK (Try397)), the active protein kinase B (AKT), and cell division cycle 42 (CDC42) were significantly reduced. Besides, Batatasin III significantly suppressed EMT indicated by the decrease of N-cadherin and Vimentin, and up-regulation of E-cadherin. Conclusion: Batatasin III has anti-cancer activities; inhibits cancer migration and invasion by suppressing EMT. Our findings establish Batatasin III as a potential compound for further studies aimed at finding a better, more effective treatment approach for lung cancer.

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Development and In Vitro Characterization of a Gemcitabine-loaded MUC4-targeted Immunoliposome Against Pancreatic Ductal Adenocarcinoma

Background/Aim: Pancreatic Ductal adeno-carcinoma (PDAC) is a devastating disease. Gemcitabine is the standard chemotherapeutic agent against PDAC but has only limited effectiveness. The aim of the study was to develop and study the targeting affinity and in vitro antiproliferative effect of a MUC4-targeted gemcitabine-loaded immuno-liposome for treatment of PDAC. Materials and Methods: Gemcitabine-loaded immunoliposomes were developed by grafting anti-MUC4 antibodies to the liposomal surface. Targeting affinity was compared in vitro between immunoliposomes and non-targeted liposomes and anti-proliferative effect was compared in vitro between free drug, non-targeted liposomal gemcitabine and MUC4-targeted immunoliposomal gemcitabine on a MUC4-positive pancreatic cancer cell line, Capan-1. Results: Development of a MUC4-targeted immunoliposome was confirmed and characterized by immunoblots and size characterization. The MUC4-targeted immunoliposome showed a significantly higher targeting affinity compared to the non-targeted liposomes and also showed an improved antiproliferative effect compared to free and non-targeted liposomal drug. Conclusion: Successful development and characterization of a MUC4-targeted immunoliposome shows promising results for a targeted treatment and improved retention of gemcitabine for treatment of PDAC.

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Effect of Tumor Microenvironment on Selective Uptake of Boric Acid in HepG2 Human Hepatoma Cells

Background: Feasibility and efficacy of boric acid (BA)-mediated boron neutron capture therapy (BNCT) was first demonstrated by eliminating hepatocellular carcinoma (HCC) in a rat model. Furthermore, selective uptake of BA by liver tumor cells was shown in a rabbit model. To gain further insight, this study aimed to investigate the mechanisms of transportation and selective uptake of BA in HepG2 liver tumor cells. Materials and Methods: Transportation of BA in HepG2 cells was analyzed by time-course assays and by analyzing the rate of diffusion versus the concentration of BA. The effect of different tumor conditions on BA uptake was studied by treating HepG2 cells with 25 μg ¹⁰B/ml BA under different concentrations of glucose, at different pH and in the presence of water-soluble cholesterol. Results: HepG2 cells mainly uptake BA by simple diffusion. Cell membrane permeability may also contribute to tumor-specific uptake of BA. Conclusion: The selective uptake of BA was achieved primarily by diffusion, while other factors, such as low pH and increased membrane fluidity, which are hallmarks of HCC, might further enhance BA uptake.

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Fucoidans Stimulate Immune Reaction and Suppress Cancer Growth

Background/Aim: Fucoidans are gaining popularity as natural immunomodulators. The aim of this study was to compare the immunological activities or both purified samples and commercially available mixtures containing fucoidan. Materials and Methods: We evaluated the effects of various samples on phagocytosis, mitogenic response, natural killer (NK) activity, antibody formation and inhibition of breast cancer growth. Results: We found significant immunostimulating activity, but the strength of these effects was different among individual samples. Conclusion: Fucoidans have strong immunostimulating potential, including inhibition of cancer, with isolated samples offering better activity than commercial mixtures.

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Association of visitation policy and health care-acquired respiratory viral infections in hospitalized children

Publication date: Available online 19 October 2017
Source:American Journal of Infection Control
Author(s): Matthew Washam, Jon Woltmann, Andrea Ankrum, Beverly Connelly
Visitor restriction policies are meant to prevent health care-acquired viral infections; however, data on their efficacy in hospitalized children are limited. We report a 37% reduction in health care-acquired respiratory viral infections in a children's hospital following standardization of the visitation policy that limited the number of visitors during a patient's hospitalization.



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Molecular Interactions of Carcinogenic Aromatic Amines, 4-Aminobiphenyl and 4,4-Diaminobiphenyl, with Lactoperoxidase - Insight to Breast Cancer

Background/Aim: Lactoperoxidase (LPO) is an antimicrobial protein present in milk, saliva, gastric secretions, tears and upper respiratory tract secretions. LPO constitutes an important enzyme of the human immune defense system. However, LPO has also been suggested to be involved in breast cancer etiology through production of reactive free radicals and activation of carcinogenic aromatic compounds. Aromatic compounds are generally highly lipophilic and thus accumulate in highly fatty breast tissues. The aromatic compounds 4-aminobiphenyl (ABP) and 4,4'-diaminobiphenyl (BZ) are known to have carcinogenic properties. LPO catalyzes their oxidation and converts them into reactive products which bind to DNA and form adducts. These DNA adducts subsequently lead to breast cancer. Materials and methods: The crystal structure of LPO was obtained from Protein Data Bank. Structures of ABP and BZ were retrieved from PubChem database. Induced Fit Docking was performed using glide module from Schrodinger. Results: The present study reports the structural binding of ABP and BZ with LPO using in silico approaches. The amino acid residues of LPO involved in the binding with the two aromatic ligands were characterized and binding energy values were calculated. Conclusion: Both ABP and BZ were placed in the substrate binding site present in the distal heme cavity of LPO with good affinity. The binding mode mimicked that of the natural substrate since these compounds did not disturb the water molecule that plays an important role in the oxidation reaction. Thus, the water molecule is potentially available for facilitating the subsequent activation of the aromatic amines to reactive species which may form DNA adducts leading to breast cancer.

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Patient and health care worker perceptions of daily use of ultraviolet-C technology as an adjunct to daily cleaning in an academic hospital: Secondary study of Ultra Violet-C Light Evaluation as an Adjunct to Removing Multi-Drug Resistant Organisms

Publication date: Available online 19 October 2017
Source:American Journal of Infection Control
Author(s): Clare Rock, Melanie S. Curless, Kathryn A. Carson, Elaine Nowakowski, Verna Scheeler, Lisa L. Maragakis
A cluster randomized crossover trial is in progress at The Johns Hopkins Hospital to investigate the impact of daily ultraviolet (UV)-C light disinfection on the acquisition of health care–associated pathogens. To understand perceptions and challenges to daily use of UV-C, we surveyed health care workers (HCWs) and patients. Most HCWs think daily UV-C decreases the patients' risk of acquiring infection. Daily UV-C is acceptable to patients and may enhance their overall hospital experience.



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BMI1 Inhibitors Down-regulate NOTCH Signaling and Suppress Proliferation of Acute Leukemia Cells

Background/Aim: B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is up-regulated in several cancers; therefore, we investigated the effects of BMI1 inhibitors on leukemia cells. Materials and Methods: Four acute myeloid leukemia and two T-lymphoblastic leukemia cell lines were treated with BMI1 inhibitors artemisinin, PRT4165, and PTC-209 and analyzed for cell proliferation and gene expression by microarray and immunoblotting. Results: PTC-209 and PRT4165 suppressed the growth of all cell lines through apoptosis.Artemisinin acted only on Jurkat cells. BMI1 inhibitors and BMI1-specific siRNA down-regulated the expression of NOTCH signaling proteins NOTCH1, HES1, and MYC. All but one cell lines did not have the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene targeted by BMI1, thus the inhibitors acted through CDKN2A-independent pathways. Conclusion: BMI1 inhibition suppressed proliferation of leukemia cells through NOTCH signaling which functions downstream of BMI1, suggesting that BMI1 inhibitors can be candidate targeted drugs against leukemia.

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Impact of home versus hospital dressing on bacterial contamination of surgical scrubs in the obstetric setting: A randomized controlled trial

Publication date: Available online 19 October 2017
Source:American Journal of Infection Control
Author(s): Darcy H. Slizewski, Emily Heberlein, Jennifer F. Meredith, Laura Beth Jobe, Kacey Y. Eichelberger
BackgroundThe impact of the site where an obstetrician dresses in their surgical scrubs, home versus hospital, on total bacterial burden remains unknown. Therefore, our objective was to quantify the effect of dressing in surgical scrubs at home versus at the hospital on the bacterial contamination at the beginning of a scheduled shift.MethodsThis was a single blind randomized controlled trial. Eligible participants were resident physicians assigned to labor and delivery at a single institution during the study period, and participants were randomized daily to 1 of 4 arms based on the site where their scrubs were laundered (A) and where the resident dressed (B) (A/B): home/home, home/hospital, hospital/home, and hospital/hospital. At the beginning of the assigned shift, microbiologic samples from the chest pocket and pants' tie were collected with a sterile culture swab. Samples were plated on trypticase soy agar with 5% sheep blood before being incubated at 35°C-37°C for 48 hours, with observation every 24 hours. The primary outcome was total bacterial burden, defined as the sum of the colony forming units (CFUs) from the 2 sampling sites.ResultsThere were 21 residents randomized daily for 4 days to 1 of 4 study arms, resulting in 84 observations. There were no baseline differences between the home- and hospital-dressed cohorts. Overall, 68% of sampled scrubs demonstrated some bacterial growth. There was no difference between the home- and hospital-dressed cohorts in percentage of samples demonstrating any bacterial growth after 72 hours (60% vs 76%, P = .14), nor in median bacterial burden at the beginning of a shift (2 [interquartile range, 0-7] vs 1 [interquartile range, 1-5] CFUs, P = .62). Finally, there was no difference in total bacterial burden at the beginning of a shift between the home- and hospital-dressed cohorts when stratified by site where the scrubs were laundered.ConclusionsThere was no significant difference in total bacterial burden of surgical scrubs at the start of a shift between cohorts who dressed at home versus at the hospital.



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Orlistat Reduces Proliferation and Enhances Apoptosis in Human Pancreatic Cancer Cells (PANC-1)

Background/aim: Pancreatic cancer is a disease with very poor prognosis, and none of currently available pharmacotherapies have proven to be efficient in this indication. The aim of this study was to analyze the expression of fatty acid synthase (FASN) gene as a potential therapeutic target in proliferating human pancreatic cancer cells (PANC-1), and verify if orlistat, originally developed as an anti-obesity drug, inhibits PANC-1 proliferation. Materials and Methods: The effects of orlistat on gene expression, lipogenesis, proliferation and apoptosis was studied in PANC-1 cell culture. Results: Expression of FASN increased during proliferation of PANC-1. Inhibition of FASN by orlistat resulted in a significant reduction of PANC-1 proliferation and enhanced apoptosis of these cells. Conclusion: This study showed, to our knowledge for the first time, that orlistat exhibits significant antitumor activity against PANC-1 cells. This implies that orlistat analogs with good oral bioavailability may find application in pharmacotherapy of pancreatic cancer.

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Hospital readmissions related to Clostridium difficile infection in the United States

Publication date: Available online 16 October 2017
Source:American Journal of Infection Control
Author(s): Abhishek Deshpande, Chaitanya Pant, Mojtaba Olyaee, Curtis J. Donskey
Using a national readmissions database, we report a significant burden of Clostridium difficile–associated readmissions in the United States manifested as a high rate of rehospitalizations and substantial hospital stays and costs.



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