Characteristics of size-resolved atmospheric inorganic and carbonaceous aerosols in urban Shanghai

Publication date: October 2017
Source:Atmospheric Environment, Volume 167
Author(s): X.X. Ding, L.D. Kong, C.T. Du, A. Zhanzakova, H.B. Fu, X.F. Tang, L. Wang, X. Yang, J.M. Chen, T.T. Cheng
Size-segregated aerosol particles were collected with a 10-stage Micro-Orifice Uniform Deposit Impactor (MOUDI) at an urban site in Shanghai, China for four non-consecutive months representing four seasons from 2015 to 2016. Chemical composition, including water-soluble ions as well as organic carbon (OC), elemental carbon (EC) and secondary organic carbon (SOC) of size-resolved (0.056–18 μm) atmospheric aerosols in four seasons and in different polluted cases were studied. The size distributions of sulfate, nitrate and ammonium (SNA) and carbonaceous aerosol (OC, EC and SOC) were discussed and the potential sources of PM1.8-associated secondary species (SO4²⁻, NO3⁻, SNA and SOC) in different seasons were identified by potential source contribution function (PSCF) model. Results showed that atmospheric ultrafine and fine particle pollution in Shanghai were very serious during the study period. Most of the water-soluble ions tended to be enriched in fine particles, especially being abundant in the droplet mode in polluted cases. Compared with sulfate, size distributions of nitrate and ammonium presented more significant seasonal variations and showed distinctive characteristics in polluted days. Abundant nitrate was concentrated in fine particles in cold seasons (spring and winter), whereas it was enriched in coarse mode during summer and autumn. The droplet mode sulfate with high concentration did not result in the aggravation of air pollution, while the nucleation mode sulfate may have made a great contribution to the air pollution in urban Shanghai. It was also found that the formation of air pollution in urban Shanghai had a significant link with nitrate and ammonium, especially with nitrate and ammonium in condensation mode and droplet mode, and the contribution of sulfate to the pollution formation in Shanghai would somehow be surpassed by the increasing nitrate and ammonium. OC and EC concentrations from spring to winter were found to be 11.10, 7.10, 12.30, 20.16, and 3.73, 2.84, 4.63, 7.10 μg m⁻³, respectively, distinctly presenting the summer minima and winter maxima in this study. The maximum OC/EC was in the droplet mode and the minimum was in the nucleation mode for both clean and polluted days. The great contribution of SOC to OC in droplet mode and the occurrence of PM pollution necessarily had an important bearing on the SOC formation in droplet mode particles. Particle acidity may play a key role in secondary organic aerosol formation and the particles with the size of 0.056–0.1 μm was the most sensitive particles to acid catalysis in SOA formation. The similar PSCF results of PM1.8-associated SOC to those of SO4²⁻, NO3⁻ and SNA indicated possible connections between the formation of SOC and secondary inorganic species in PM.

Graphical abstract

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Fluorescence spectroscopy in the visible range for the assessment of UVB radiation effects in hairless mice skin

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Carolina de Paula Campos, Camila de Paula D'Almeida, Marcelo Saito Nogueira, Lilian Tan Moriyama, Sebastião Pratavieira, Cristina Kurachi
Ultraviolet (UV) radiation may induce skin alterations as observed in photoaging. Some recognized modifications are epidermal hyperplasia, amorphous deposition of degraded elastic fibers and reduction in the number of collagen fibers. They alter the tissue biochemical properties that can be interrogated by steady state fluorescence spectroscopy (SSFS). In this study, we monitored the changes in endogenous fluorescence emission from hairless mice skin during a protocol of photoaging using UVB irradiation. To perform the fluorescence spectroscopy, it was used a violet laser (408nm) to induce the native fluorescence that is emitted in the visible range. Under 408nm excitation, the emission spectrum showed bands with peaks centered around 510, 633 and 668nm for irradiated and control groups. A relative increase of the fluorescence at 633nm emission on the flank was observed with time when compared to the ventral skin at the same animal and the non-irradiated control group. We correlated the emission at 633nm with protoporphyrin IX (PpIX), and our hypothesis is that the PpIX metabolism in the photoaged and aged skin are different. PpIX fluorescence intensity in the photoaged skin is higher and more heterogeneous than in the aged skin. Notwithstanding, more spectroscopic and biochemistry studies investigating the 510 and 633nm emission are needed to confirm this hypothesis.



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Periopathogens differ in terms of the susceptibility to toluidine blue O-mediated photodynamic inactivation

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Zuzanna Oruba, Przemysław Łabuz, Wojciech Macyk, Maria Chomyszyn-Gajewska
BackgroundThe main goal of periodontal therapy is to eliminate the infection spreading in periodontium. Antimicrobial photodynamic therapy may be applied in order to eradicate pathogens remaining in periodontal tissues after conventional mechanical debridement, to improve the treatment results. The aim of this in vitro study was to evaluate the susceptibility of selected key periopathogens to toluidine blue O-mediated photodynamic inactivation and the influence of photosensitizer's concentration and light dose on the effectiveness of this process.MethodsFollowing bacterial strains were used in the experiments: Porphyromonas gingivalis ATCC 33277, Aggregatibacter actinomyctemecomitans ATCC 33384, Fusobacterium nucleatum ATCC 10953. Toluidine blue O (TBO) was used in concentration ranging from 0.004 to 0.5mg/mL. Irradiation was performed by a non-laser red light source.ResultsComplete eradication of P. gingivalis was obtained upon the application of TBO in the concentration of 0.1mg/mL and the highest light dose. A, actinomycetemcomitans was, in turn, not susceptible to photodynamic inactivation regardless of the dosimetric parameters applied. High viability reductions were also obtained for F. nucleatum, however no complete eradication. The effectiveness of photodynamic inactivation of susceptible periopathogens was dependent on the light dose and photosensitizer's concentration.ConclusionsPeriopathogens differ in terms of their susceptibility to photodynamic inactivation. Antimicrobial PDT may be valuable in the treatment of those cases of periodontal disease, in which P. gingivalis is a dominating pathogen. Microbiological examination prior to clinical application of aPDT may be recommended.



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Impact of genotypic and phenotypic differences in sarcoma models on the outcome of photochemical internalization (PCI) of bleomycin

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Cathrine Elisabeth Olsen, Simen Sellevold, Theodossis Theodossiou, Sebastian Patzke, Kristian Berg
The low curative response to current treatment regimens for most soft tissue sarcomas indicates a strong need for alternative treatment strategies and predictive markers for treatment outcome. PCI (photochemical internalization) is a novel treatment strategy to translocate drugs into cytosol that otherwise would have been degraded in lysosomes. Two highly geno-and phenotypically different uterine and vulvar leiomyosarcoma cell lines, MES-SA and SK-LMS-1, were treated with bleomycin (BLM) activated by PCI (PCIBLM). The MES-SA cells were much more sensitive to PCIBLM than the SK-LMS-1 cells and the treatment induced a 7–8 fold higher increase in DNA double-strand breaks at the same dose of light as measure by γH2AX staining. A 3-fold higher induction of apoptosis and stronger activation of Bax and p21 was also measured in the P53WT MES-SA cells, compared to the P53mut SK-LMS-1 cells. The basal formation of reactive oxygen species (ROS) was 3-fold higher in SK-LMS-1 cells than in the MES-SA cells and SK-LMS-1 cells expressed glutathione peroxidase 1 (GPx1) and more superoxide dismutase 2 (SOD2) than the MES-SA cells. Glutathione depletion with the glutathione synthetase inhibitor buthionine sulfoximine increased the cytotoxic effect of the photochemical treatment (PDT) most strongly in the SK-LMS-1 cells, and reduced PCIBLM-induced H2AX activation in the MES-SA cells, but not in the SK-LMS-1 cells. The results indicate PCIBLM as a potential novel treatment strategy for soft tissue sarcomas, with antioxidant enzymes, in particular GPx1, and the P53 status as potential predictive markers for response to PCIBLM.

Graphical abstract

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Contrast enhanced ultrasound imaging can predict vascular-targeted photodynamic therapy induced tumor necrosis in small animals

Publication date: Available online 5 September 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): F.H. Cornelis, K. Kim, J.C. Durack, S. Jebiwott, A. Scherz, G. Srimathveeravalli, J.A. Coleman
AimsTo evaluate the accuracy of contrast-enhanced ultrasound (CEUS) for monitoring tumor necrosis following WST-11 vascular targeted photodynamic therapy (VTP) using imaging-pathology correlation.MethodsRenal adenocarcinoma cells were injected into the hindlimb of 13 BalB/c mice resulting in tumors ranging from 9.8 to 194.3mm³. US guidance was used to place a laser fiber into the tumor, and VTP was performed. CEUS was performed prior to animal sacrifice, 24hours post-VTP. Whole tumors were extracted for histopathologic analysis using H&E and TUNEL staining. Pathology samples corresponding to the CEUS imaging plane were prepared in order to compare the size and extents of tumor necrosis.ResultsTumor necrosis following VTP appeared as a central region of non-enhancement on CEUS, while viable tumor appeared as patchy regions of enhancement in the tumor periphery. The region of tumor necrosis measured in mean 66% and 64.8% of total tumor area on CEUS and pathology respectively (p=0.2). The size and location of the necrosis on CEUS images and pathology samples were found correlative with no inter-observer difference (weighted kappa of 0.771 and 0.823, respectively).ConclusionCEUS allows accurate monitoring of VTP induced tumor necrosis in a small animal model.



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Efficacy of Erythrosine and Cyanidin-3-glucoside Mediated Photodynamic Therapy on Porphyromonas Gingivalis Biofilms using Green Light Laser.

Publication date: Available online 5 September 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Aroon Teerakapong, Teerasak Damrongrungruang, Sajee Sattayut, Noppawan Phumala Morales, Surada Tantananugool
BackgroundThe purpose of this in vitro study was to evaluate the efficacy of erythrosine and cyanidin-3-glucoside as photosensitizers in PDT for the elimination of Porphyromonas gingivalis (P. gingivalis) biofilms.MethodsP. gingivalis biofilms were prepared from a chronic periodontitis subject. Erythrosine and cyanidin-3-glucoside were prepared and randomly allocated as follows: 110, 220, 330, and 440μM erythrosine; 101, 202, 303, and 404μM anthocyanin; and 440μM erythrosine+404μM cyanidin-3-glucoside. There were 18 PDT experimental groups (non-irradiated/irradiated with a 532-nm green light diode laser at 1.29J/cm² for 60seconds). The 3 controls were grouped as follows: biofilms exposed to the photosensitizers alone, biofilms exposed to the laser alone, and biofilms exposed to 0.12% chlorhexidine. All sample groups were cultured at 1, 3 and 6hrs after PDT and incubated in an anaerobic chamber at 37°C for 4 days. The surviving fraction was calculated from the log10 CFU/ml. The 330 and 440μM erythrosine and the 440μM erythrosine+404μM cyanidin-3-glucoside were mixed with spin traps (TEMPO, DMPO), and the electron spin resonance spectra were evaluated.ResultsThe log10 CFU/ml measurements showed that the PDT groups with 330μM or 440μM erythrosine and 440μM erythrosine+404μM cyanidin-3-glucoside had statistically significant differences from the other groups (one-way ANOVA and Bonferroni's multiple comparison test, p- value≤0.05).ConclusionsPDT using 330μM erythrosine, 440μM erythrosine or 440μM erythrosine+404μM cyanidin-3-glucoside irradiated with the laser more effectively inhibited P. gingivalis in biofilms.



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The histone lysine methyltransferase Ezh2 is required for maintenance of the intestine integrity and for caudal fin regeneration in zebrafish

Publication date: Available online 5 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Barbara Dupret, Pamela Völkel, Constance Vennin, Robert-Alain Toillon, Xuefen Le Bourhis, Pierre-Olivier Angrand
The histone lysine methyltransferase EZH2, as part of the Polycomb Repressive Complex 2 (PRC2), mediates H3K27me3 methylation which is involved in gene expression program repression. Through its action, EZH2 controls cell-fate decisions during the development and the differentiation processes. Here, we report the generation and the characterization of an ezh2-deficient zebrafish line. In contrast to its essential role in mouse early development, loss of ezh2 function does not affect zebrafish gastrulation. Ezh2 zebrafish mutants present a normal body plan but die at around 12 dpf with defects in the intestine wall, due to enhanced cell death. Thus, ezh2-deficient zebrafish can initiate differentiation toward the different developmental lineages but fail to maintain the intestinal homeostasis. Expression studies revealed that ezh2 mRNAs are maternally deposited. Then, ezh2 is ubiquitously expressed in the anterior part of the embryos at 24 hpf, but its expression becomes restricted to specific regions at later developmental stages. Pharmacological inhibition of Ezh2 showed that maternal Ezh2 products contribute to early development but are dispensable to body plan formation. In addition, ezh2-deficient mutants fail to properly regenerate their spinal cord after caudal fin transection suggesting that Ezh2 and H3K27me3 methylation might also be involved in the process of regeneration in zebrafish.

Graphical abstract

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Concurrent uptake and metabolism of dyestuffs through bio-assisted phytoremediation: a symbiotic approach

Abstract

Manipulation of bio-technological processes in treatment of dyestuffs has attracted considerable attention, because a large proportion of these synthetic dyes enter into natural environment during synthesis and dyeing operations that contaminates different ecosystems. Moreover, these dyestuffs are toxic and difficult to degrade because of their synthetic origin, durability, and complex aromatic molecular structures. Hence, bio-assisted phytoremediation has recently emerged as an innovative cleanup approach in which microorganisms and plants work together to transform xenobiotic dyestuffs into nontoxic or less harmful products. This manuscript will focus on competence and potential of plant-microbe synergistic systems for treatment of dyestuffs, their mixtures and real textile effluents, and effects of symbiotic relationship on plant performances during remediation process and will highlight their metabolic activities during bio-assisted phytodegradation and detoxification.

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Role of an estradiol regulatory factor-hydroxysteroid dehydrogenase (HSD) in Toxoplasma gondii infection and pathogenicity

Publication date: Available online 5 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Xiao Zhang, Jing Liu, Muzi Li, Yong Fu, Taotao Zhang, Qian Han, Qun Liu
Toxoplasma gondii is an apicomplexan parasite that infects most species of warm-blooded animals, including humans, and causes abortions and severe damage to the fetal central nervous system. During pregnancy, the prevalence of toxoplasmosis increases throughout the second and third quarter of gestation, while the hormones progesterone and estradiol simultaneously increase. Thus, it has been suggested that these hormones could affect parasite reproduction. This study was mainly focused on an estradiol regulatory factor-Hydroxysteroid dehydrogenase (HSD) gene in T. gondii.Our data showed that estradiol promoted Pru (Type II) and VEG (Type III) infection and thus significantly contributed to the pathogenicity of T. gondii in mice. Subsequently, we found that this phenomenon may relate to the interplay of T. gondii and estradiol. We reported that estradiol can enter T. gondii tachyzoites. Bioinformatics analysis showed that T. gondii may have a residual estradiol metabolism-related gene HSD. To verify the gene function, HEK293T cells were transiently transfected with Tg-HSD and gene expression was induced. Then, HPLC (high-performance liquid chromatography) analysis showed that Tg-HSD can efficiently transform estrone into estradiol. Moreover, Tg-HSD −overexpressing parasites showed significantly enhanced pathogenicity and upregulation of estradiol levels in mice. In conclusion, estradiol can promote T. gondii infection in vitro and in vivo, and this may be related to its Tg- HSD gene.



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Salad bar selection patterns of elementary school children

Publication date: 1 January 2018
Source:Appetite, Volume 120
Author(s): Geraldine Moreno-Black, Jean Stockard
From the perspective of child-focused nutrition research, the analysis of the school cafeteria culture and environment is critical. Most children eat at least one meal at school per school day, thus elementary schools are a good setting for influencing the early development of healthy eating habits. The salad bar in particular has gained attention as a means of increasing fruit and vegetable consumption. The purpose of the present study was to provide insight about the types of items children choose or do not choose from the salad bar. Our aims were to document elementary school children's food selection patterns by examining photographs of 2903 cafeteria trays. Our results show students in this study took very few items – and a substantial number did not take any at all. We examined three factors, gender, grade, and item placement, in relation to food selection. Gender was the most significant factor, with girls being more likely to choose both fruits and vegetables. Students in lower grades were more likely to select vegetables and to choose more of them. Finally, item placement did not affect choice. Our findings lead us to suggest the importance of integrating information about fruits and vegetables into the school curriculum and that schools strongly consider which items to offer because our results indicate children consistently do not choose certain items and probably do not conceive of them in the context of the adult concept of a salad. Finally, because a child's choice of food is not always a simple act we suggest ethnographic research on how children perceive and use salad bars would provide important insight into the value of retaining or expanding salad bars in elementary schools.



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Understanding Immunity through the Lens of Disease Ecology

Publication date: Available online 4 September 2017
Source:Trends in Immunology
Author(s): Stephen M. Hedrick
As we describe the immune system in ever more exquisite detail, we might find that no matter how successful, this approach will not be sufficient to understand the spread of infectious agents, their susceptibility to vaccine therapy, and human disease resistance. Compared with the strict reductionism practiced as a means of characterizing most biological processes, I propose that the progression and outcome of disease-causing host–parasite interactions will be more clearly understood through a focus on disease ecology.



http://ift.tt/2gEnw3R

Influence of soil physical properties and vegetation coverage at different slope aspects in a reclaimed dump

Abstract

Vegetation coverage is an important parameter for affecting soil erosion and the physical and chemical properties of soil. To analyze the mutual influence between vegetation coverage and soil quality at different slope aspects in a reclaimed dump, fitting analyses were built between the normalized difference vegetation index and soil physical properties at each slope aspect. Twenty six quadrats were sampled in slope-platform alternate mode. Each quadrat was 10 m × 10 m. Vegetation index and soil physical properties were measured and calculated. Through curve fitting analysis, the results showed that soil bulk density has a negative correlation with the vegetation index on shady and half shady slopes, sunny slopes, and half sunny slopes. Soil porosity has a positive correlation with the vegetation index on shady and half shady slopes, sunny slope, and half sunny slope. The soil mass water content has a concave function relationship with the vegetation index on shady and half shady slopes and has a quadratic function relationship with the vegetation index on sunny and half sunny slopes, with the parabola moving upwards. The soil gravel content has a linear relationship with the vegetation index on shady and half shady slopes, and the image has a negative slope with a quadratic function relationship to the vegetation index on sunny slope and half sunny slope, with the parabola moving downwards. Due to differences among hydrothermal conditions, the relationship between vegetation coverage and soil quality indicators at different slope aspects is different; therefore, reasonable improvement of soil quality indicators on sunny and half sunny slopes could help plants to grow. These findings feed into a reference document that sets out how vegetation and soil quality may be improved in mining areas.

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Ecotoxicity and antibiotic resistance of a mixture of hospital and urban sewage in a wastewater treatment plant

Abstract

Hospital and urban effluents are a source of diverse pollutants such as organic compounds, heavy metals, detergents, disinfectants, pharmaceuticals, and microorganisms resistant to antibiotics. Usually, these two types of effluent are mixed in the sewage network, but a pilot site in France now allows studying them separately or mixed to understand more about their characteristics and the phenomena that occur following their mixing. In this study, their ecotoxicity (Daphnia magna mobility, Pseudokirchneriella subcapitata growth, Brachionus calyciflorus reproduction, and SOS Chromotest) and antibiotic resistance (integron quantification) were assessed during mixing and treatment steps. The main results of this study are (i) the ecotoxicity and antibiotic resistance potentials of hospital wastewater are higher than in urban wastewater and (ii) mixing two different effluents does not lead to global synergistic or antagonistic effects on ecotoxicity and antibiotic resistance potential. The global additivity effect observed in this case must be confirmed by other studies on hospital and urban effluents on other sites to improve knowledge relating to this source of pollution and its management.

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The effect of substrate/inoculum ratio on the kinetics of methane production in swine wastewater anaerobic digestion

Abstract

Methane production from swine wastewater was evaluated by using sewage sludge as inoculum in three substrate to inoculum ratios (SIRs) named A (1:1), B (3:1) and C (6:1), with the objective to identify the proportion that optimizes the performance of the process. Duplicated batch bioreactors of 1 L capacity under mesophilic conditions were used to carry out the experiment. The highest biogas yield was observed in A treatment (554 ± 75 mL/g volatile solid (VS)). Cumulative methane production decreased from 382 ± 22 to 232 ± 5 mL/g VS when SIR increased from 1:1 to 6:1. The first-order model and the modified Gompertz equation were used to model the experimental cumulative methane yield giving adjustments with coefficients of determination of 96 and 99% respectively. The effect of the SIR was analysed based on the kinetic parameters of the Gompertz equation, which are methane production potential, maximum methane production rate and lag-phase time. The best performance in terms of the kinetic parameters was obtained for treatment A; however, treatment B could still ensure a stable process. The use of higher inoculum concentration generated 463.1% higher methane production rate and required 77.3% shorter adaptation time (lag phase) in the SIR range studied. When higher SIR was used (e.g. 14:1, previous work), it could be observed that the Gompertz equation also adjusted adequately the experimental data (R ² > 0.99) although the lag-phase time did not remain in a linear relationship with SIR but exponentially above SIR = 6:1. These results demonstrated that when a low amount of inoculum was used, the adaptation time of microorganisms resulted much higher than expected delaying the methane production and extending the time needed to achieve adequate performance of the process.

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Subretinal fibrin absorption after 577-nm subthreshold micropulse laser therapy in a CSC case: a brief report

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How extreme dieting becomes compulsive: a novel hypothesis for the role of anxiety in the development and maintenance of anorexia nervosa

Publication date: Available online 5 September 2017
Source:Medical Hypotheses
Author(s): E.C. Lloyd, A.M. Haase, B. Verplanken, I. Frampton
The US National Institute of Mental Health's Research Domain Criteria (NIMH RDoC) advocates the study of features common to psychiatric conditions. This transdiagnostic approach has recently been adopted into the study of anorexia nervosa (AN), an illness that can be considered compulsive in nature. This has led to the development of an account of AN that identifies key roles for the heightened reinforcement of starvation, leading to its excessive repetition, and goal-directed system dysfunction. Continuing to consider models of illness in other compulsive disorders, we extend the existing account to explain the emergence of reinforcement and goal-directed system abnormalities in AN, proposing that anxiety is central to both processes. As such we emphasise the particular importance of the anxiolytic effects of starvation, over other reinforcing outcomes, in encouraging the continuation of starvation within a model that proposes a number of mechanisms by which anxiety operates. We suggest the psychopathology of AN mediates the relationship between the anxiolytic effects of starvation and excessive repetition of starvation, and that compulsive starvation has reciprocal effects on other factors of the model. We thus account for the emergence of symptoms of AN other than compulsive starvation, and for the relationship between different features of the disorder. By extending and adapting an existing explanation of AN, we provide a richer aetiological model that invites new research questions and could inform novel approaches to prevention and treatment.



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Anti-HIV activity of southern African plants: Current developments, phytochemistry and future research

Publication date: 10 January 2018
Source:Journal of Ethnopharmacology, Volume 210
Author(s): Gerhard Prinsloo, Cynthia K. Marokane, Renée A. Street
Ethnopharmacological relevanceThe African continent is home to a large number of higher plant species used over centuries for many applications, which include treating and managing diseases such as HIV. Due to the overwhelming prevalence and incidence rates of HIV, especially in sub-Saharan Africa, it is necessary to develop new and affordable treatments.Aim of the studyThe article provides an extensive overview of the status on investigation of plants from the southern African region with ethnobotanical use for treating HIV or HIV-related symptoms, or the management of HIV. The review also provide an account of the in vitro assays, anti-viral activity and phytochemistry of these plants.Materials and methodsPeer-reviewed articles investigating plants with ethnobotanical information for the treatment or management of HIV or HIV-related symptoms from the southern African region were acquired from Science Direct, PubMed central and Google Scholar. The selection criteria was that (1) plants should have a record of traditional/popular use for infectious or viral diseases, HIV treatment or symptoms similar to HIV infection, (2) if not traditionally/popularly used, plants should be closely related to plants with popular use and HIV activity identified by means of in vitro assays, (3) plants should have been identified scientifically, (4) should be native to southern African region and (5) anti-HIV activity should be within acceptable ranges.ResultsMany plants in Africa and specifically the southern African region have been used for the treatment of HIV or HIV related symptoms and have been investigated suing various in vitro techniques. In vitro assays using HIV enzymes such as reverse transcriptase (RT), integrase (IN) and protease (PR), proteins or cell-based assays have been employed to validate the use of these plants with occasional indication of the selectivity index (SI) or therapeutic index (TI), with only one study, that progressed to in vivo testing. The compounds identified from plants from southern Africa is similar to compounds identified from other regions of the world, and the compounds have been divided into three groups namely (1) flavonoids and flavonoid glycosides, (2) terpenoids and terpenoid glycosides and (3) phenolic acids and their conjugated forms.ConclusionsAn investigation of the plants from southern Africa with ethnobotanical use for the treatment of HIV, management of HIV or HIV-related symptoms, therefore provide a very good analysis of the major assays employed and the anti-viral compounds and compound groups identified. The similarity in identified anti-viral compounds worldwide should support the progression from in vitro studies to in vivo testing in development of affordable and effective anti-HIV agents for countries with high infection and mortality rates due to HIV/AIDS.

Graphical abstract

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Extracts of Equisetum giganteum L and Copaifera reticulate Ducke show strong antiviral activity against the sexually transmitted pathogen herpes simplex virus type 2

Publication date: 10 January 2018
Source:Journal of Ethnopharmacology, Volume 210
Author(s): Marianela Patzi Churqui, Liza Lind, Karolina Thörn, Alexandra Svensson, Otto Savolainen, Katty Terrazas Aranda, Kristina Eriksson
Ethnopharmacological relevanceEquisetum giganteum L and Copaifera reticulate Ducke have been traditionally used by women of the Tacana tribe in the Bolivian Amazonas for genital hygiene and for treatment of genital infection/inflammation.Aim of the studyTo assess the ability of extracts from Equisetum giganteum L and Copaifera reticulate Ducke to block genital viral infection by herpes simplex virus type 2.Materials and MethodsEquisetum giganteum L and Copaifera reticulate Ducke were collected from the Amazon region of La Paz, Bolivia. Extracts were prepared and screened for anti-viral activity against herpes simplex virus type 2 (HSV-2) using both in vitro and in in vivo models of infection.ResultsEquisetum giganteum L and Copaifera reticulate Ducke efficiently blocked HSV-2 infection of cell cultures without major cell cytotoxic effects. Extracts of Equisetum giganteum L and Copaifera reticulate Ducke could prevent HSV-2 disease development when administered together with virus in a mouse model of genital HSV-2 infection. In vitro analyses revealed that both plant extracts exerted their anti-HSV-2 effects by interfering with viral cell attachment and entry, but could not block viral replication post entry.ConclusionsThese studies show that extracts of Equisetum giganteum L and Copaifera reticulate Ducke have potent antiviral activities against HSV-2 comparable to those two previously identified plants, Croton lechleri Müll. Arg. and Uncaria tomentosa (Willd. ex Schult.) DC. These studies confirm that plants used by the Tacana tribe could be explored further for the development of novel topical antiviral microbicides.

Graphical abstract

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Antiprotozoal activity of medicinal plants used by Iquitos-Nauta road communities in Loreto (Peru)

Publication date: Available online 5 September 2017
Source:Journal of Ethnopharmacology
Author(s): Pedro Vásquez-Ocmín, Sandrine Cojean, Elsa Rengifo, Soulaf Suyyagh-Albouz, Carlos A. Amasifuen Guerra, Sébastien Pomel, Billy Cabanillas, Kember Mejía, Philippe M. Loiseau, Bruno Figadère, Alexandre Maciuk
Ethnopharmacological relevanceIn the Peruvian Amazon, the use of medicinal plants is a common practice. However, there is few documented information about the practical aspects of their use and few scientific validation. The starting point for this work was a set of interviews of people living in rural communities from the Peruvian Amazon about their uses of plants. Protozoan diseases are a public health issue in the Amazonian communities, who partly cope with it by using traditional remedies. Validation of these traditional practices contributes to public health care efficiency and may help identify new antiprotozoal compounds.Aims of studyto inventory and validate the use of medicinal plants by rural people of Loreto region.Materials and methodsRural mestizos were interviewed about traditional medication of parasite infections with medicinal plants. Ethnopharmacological surveys were undertaken in two villages along Iquitos-Nauta road (Loreto region, Peru), namely 13 de Febrero and El Dorado communities. Forty-six plants were collected according to their traditional use for the treatment of parasitic diseases, 50 ethanolic extracts (different parts for some of the plants) were tested in vitro on Plasmodium falciparum (3D7 sensitive strain and W2 chloroquine resistant strain), Leishmania donovani LV9 strain and Trypanosoma brucei gambiense. Cytotoxic assessment (HUVEC cells) of the active extracts was performed. Two of the most active plants were submitted to preliminary bioguided fractionation to ascertain and explore their activities.ResultsFrom the initial plants list, 10 were found to be active on P. falciparum, 15 on L. donovani and 2 on the three parasites. The ethanolic extract from Costus curvibracteatus (Costaceae) leaves and Grias neuberthii (Lecythidaceae) bark showed strong in vitro activity on P. falciparum (sensitive and resistant strain) and L. donovani and moderate activity on T. brucei gambiense.ConclusionsThe Amazonian forest communities in Peru represents a source of knowledge on the use of medicinal plants. In this work, several extracts with antiprotozoal activity were identified. This work contributes to validate some traditional uses and opens subsequent investigations on active compounds isolation and identification.

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Trypanocidal activity of polysaccharide extract from Genipa americana leaves

Publication date: Available online 5 September 2017
Source:Journal of Ethnopharmacology
Author(s): Racquel Oliveira da Silva Souza, Paloma Leão Sousa, Ramon Róseo Paula Pessoa Bezerra de Menezes, Tiago Lima Sampaio, Louise Donadello Tessarolo, Francisca Crislandia Oliveira Silva, Maria Gonçalves Pereira, Alice Maria Costa Martins
Ethnopharmacological relevanceThe parts of the Genipa americana (Rubiaceae) tree, also known as "jenipapo" or "jenipapeiro", has been used in traditional Medicine in parasitic and bacterial infections. Thus, the experimental evolution of the antiparasitic activity of polysaccharide extracts from Genipa americana leaves, and correlation with antiparasitic and popular use is important.Aim of the studyTo evaluate the effect of polysaccharide extract obtained from Genipa americana leaves on all Trypanosoma cruzi (Y strain: benznidazole-resistant) developmental forms, a protozoan that causes Chagas' disease.Materials and MethodsAn extract rich in polysaccharides was obtained from the leaves of Genipa americana (GaEPL) by associating depigmentation in methanol followed by extraction of polysaccharides in NaOH and precipitation with ethanol. Cytotoxicity to mammalian cells (LLC-MK2) was determined using an MTT assay. Antiparasitic activity was evaluated against epimastigote, trypomastigote and amastigote forms of T. cruzi. Cell-death mechanism was determined in epimastigote forms by flow cytometry analysis after FITC-annexin V (Ax), 7-AAD, and H2DCFDA staining. Striking morphological changes were observed by scanning electron microscope.ResultsGaEPL (6.5% yield; 54.6% total carbohydrate; 21.1% uronic acid and 12% protein), inhibited all T. cruzi developmental forms, epimastigotes after periods of 24h (IC50= 740±0.075µg/mL), 48h (IC50= 710±0.053µg/mL) and 72h (IC50= 870±0.052µg/mL) of incubation; trypomastigotes (IC50= 470±0.082µg/mL) after periods of 24h and intracellular amastigotes (IC50/2 = 235 or IC50= 470µg/mL) after periods of 24 and 48h of incubation, with no toxicity on LLC-MK2 cells at the used concentrations. Analysis of the possible action mechanism in the parasites suggested cell death by necrosis with the involvement of reactive oxygen species (ROS). The scanning electron microscopy (SEM) confirmed T. cruzi death by necrosis.ConclusionsGaEPL showed significant activity against the epimastigote, trypomastigote and amastigote forms of T. cruzi, strain Y, suggesting cell death by necrosis with involvement of reactive oxygen species.

Graphical abstract

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Distribution characteristics of heavy metal(loid)s in aggregates of different size fractions along contaminated paddy soil profile

Abstract

Soil aggregates exert a significant influence on the retention and availability of heavy metal(loid)s in soil. In this study, the concentration distribution and chemical forms of heavy metals (Cu, Zn, Cd, Pb, and Hg) and a metalloid (As) in different aggregate-sized fractions (2–0.25, 0.25–0.05, 0.05–0.002, and < 0.002 mm) along the profile (0–1, 1–5, 5–15, and 15–25 cm) of a contaminated paddy field were investigated. The results showed that the values of pH, free Fe oxides (Fe_d), bulk density, and catalase activity gradually increased, whereas the soil organic matter (SOM), cation exchange capacity (CEC), electrical conductivity (EC), microbial biomass carbon (MBC), and urease activity decreased with depth. Long-term heavy metal pollution might impact the catalase activity but showed no obvious influence on the urease activity. Additionally, there was a notable difference in physicochemical properties among the soil aggregates of various particle sizes. The 2–0.25-mm fraction aggregates contained more organic matter, whereas the highest values of CEC and Fe_d were observed in the < 0.002-mm fraction. The concentrations of all six heavy metals/metalloid decreased with depth. In different layers, Cu and Cd showed the highest concentrations in the 2–0.25 mm-fraction, followed by the < 0.002-mm fraction, whereas the highest concentrations of Zn, Pb, and As appeared in the < 0.002-mm fraction. No obvious distribution regularity was observed for Hg among the aggregates. All of the metal(loid)s had lower activity in the deeper soil layers, except for Hg. Furthermore, Cu and Cd displayed more stable forms in the < 0.002-mm fraction aggregates.

http://ift.tt/2wETk0p

Age and the association of dementia related pathology with trajectories of cognitive decline

Publication date: Available online 5 September 2017
Source:Neurobiology of Aging
Author(s): Willemijn J. Jansen, Robert S. Wilson, Pieter Jelle Visser, Sukriti Nag, Julie A. Schneider, Bryan D. James, Sue E. Leurgans, Ana W. Capuano, David A. Bennett, Patricia A. Boyle
The association of dementia related pathologies with cognition is hypothesized to decrease as age advances. We examined this in 413 persons without cognitive impairment at baseline who completed annual cognitive evaluations during a mean of 10.4 years. After death, neuropathologic examinations quantified beta-amyloid plaque load, neurofibrillary tangles, and TDP-43 pathology, and identified Lewy bodies, hippocampal sclerosis, and gross and microscopic cerebral infarcts. We tested whether age at death modified associations of these neuropathologies with the nonlinear trajectory of cognitive decline using mixed-effects change point models. The rate of global cognitive decline was gradual at first and then increased approximately 10-fold in the last 3 years of life. After adjustment for all other pathologic indices, tangle density, gross infarcts, Lewy bodies, and TDP-43 were associated with global cognitive decline. However, the deleterious association of dementia related pathologies with cognitive decline did not systematically vary by age. This suggests that the neuropathologic mechanisms underlying late-life cognitive decline do not substantially differ across the spectrum of age.



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Altered intertemporal choice with age is only partially mediated by prefrontal cortex Decline of prefrontal cortical-mediated executive functions but attenuated delay discounting in aged Fischer 344 x Brown Norway hybrid rats

Publication date: Available online 5 September 2017
Source:Neurobiology of Aging
Author(s): Caesar M. Hernandez, Lauren M. Vetere, Caitlin A. Orsini, Joseph A. McQuail, Andrew P. Maurer, Sara N. Burke, Barry Setlow, Jennifer L. Bizon
Despite the fact that prefrontal cortex (PFC) function declines with age, aged individuals generally show an enhanced ability to delay gratification, as evident by less discounting of delayed rewards in intertemporal choice tasks. The current study was designed to evaluate relationships between two aspects of PFC-dependent cognition (working memory and cognitive flexibility) and intertemporal choice in young (6 mo.) and aged (24 mo.) Fischer 344 x Brown-Norway F1 hybrid rats. Rats were also evaluated for motivation to earn rewards using a progressive ratio task. As previously reported, aged rats showed attenuated discounting of delayed rewards, impaired working memory, and impaired cognitive flexibility compared to young. Among aged rats, greater choice of delayed reward was associated with preserved working memory, impaired cognitive flexibility, and less motivation to work for food. These relationships suggest that age-related changes in PFC and incentive motivation contribute to variance in intertemporal choice within the aged population. Cognitive impairments mediated by PFC are unlikely, however, to fully account for the enhanced ability to delay gratification that accompanies aging.



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Dynamic range in BOLD modulation: Lifespan aging trajectories and association with performance

Publication date: Available online 5 September 2017
Source:Neurobiology of Aging
Author(s): Kristen M. Kennedy, Maria A. Boylan, Jenny R. Rieck, Chris M. Foster, Karen M. Rodrigue
Alteration of dynamic range of modulation to cognitive difficulty has been proposed as a salient predictor of cognitive aging. Here we examine in 171 adults (aged 20-94 years) the effects of age on dynamic modulation of BOLD activation to difficulty in parametrically increasing working memory load (0-,2-,3-,4-back conditions). First, we examined parametric increases and decreases in activation to increasing WM load (positive modulation effect and negative modulation effect). Second, we examined the effect of age on modulation to difficulty (WM load) to identify regions that differed with age as difficulty increased (age-related positive and negative modulation effects). Weakened modulation to difficulty with age was found in both the positive-modulation (middle frontal, superior/inferior parietal) and negative-modulation effect (deactivated) regions (insula, cingulate, medial superior frontal, fusiform, and parahippocampal gyri, hippocampus, and lateral occipital cortex). Age-related alterations to positive modulation emerged later in the lifespan than negative modulation. Further, these effects were significantly coupled in that greater up-modulation was associated with lesser down-modulation. Importantly, greater frontal-parietal up-modulation to difficulty and greater down-modulation of deactivated regions was associated with better task accuracy and up-modulation with better working memory span measured outside the scanner. These findings suggest that greater dynamic range of modulation of activation to cognitive challenge is in service of current task performance, as well as generalizing to cognitive ability beyond the scanner task, lending support to its utility as a marker of successful cognitive aging.



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Intravenous treatment with human recombinant ApoA-I Milano reduces β-amyloid cerebral deposition in the APP23-transgenic mouse model of Alzheimer’s disease

Publication date: Available online 5 September 2017
Source:Neurobiology of Aging
Author(s): Sofía Fernández-de Retana, Alex Montañola, Paula Marazuela, Maialen De La Cuesta, Aina Batlle, Marc Fatar, Saskia Grudzenski, Joan Montaner, Mar Hernández-Guillamon
Beyond the crucial role of apolipoproteinA-I (ApoA-I) on peripheral cholesterol metabolism, this apolipoprotein has also been implicated in β-amyloid (Aβ)-related neuropathologies. ApoA-I-Milano (M) is a mutated variant, which has been shown to present increased vasoprotective properties compared to ApoA-I-wild type (wt) in models of atherosclerosis and cardiovascular damage. We speculated that ApoA-I-M may also protect Aβ–affected vasculature and reverse some of the pathological features associated with Alzheimer's disease (AD). For this purpose, we produced and characterized human recombinant ApoA-I-wt and ApoA-I-M proteins. Both of them were able to avoid the aggregation of Aβ in vitro, even though rApoA-I-M was significantly more effective in protecting endothelial cells from Aβ(1-42)-toxicity. Next, we determined the effect of chronic intravenous administration of rApoA-I-M in the APP23-transgenic mouse model of AD. We found reduced cerebral levels of Aβ(1-40) and Aβ(1-42) in mice that received rApoA-I-M, which were accompanied by a lower expression of astrocyte and microglia neuroinflammatory markers. Our results suggest an applicability of this molecule as a therapeutic candidate for protecting the brain in AD.



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Aging and a genetic KIBRA polymorphism interactively affect feedback- and observation-based probabilistic classification learning

Publication date: Available online 5 September 2017
Source:Neurobiology of Aging
Author(s): Nicolas W. Schuck, Jessica R. Petok, Martijn Meeter, Brit-Maren M. Schjeide, Julia Schröder, Lars Bertram, Mark A. Gluck, Shu-Chen Li
Probabilistic category learning involves complex interactions between the hippocampus and striatum that may depend on whether acquisition occurs via feedback or observation. Little is known about how healthy aging affects these processes. We tested whether age-related behavioral differences in probabilistic category learning from feedback or observation depend on a genetic factor known to influence individual differences in hippocampal function, the KIBRA gene (SNP rs17070145). Results showed comparable age-related performance impairments in observational as well as feedback-based learning. Moreover, genetic analyses indicated an age-related interactive effect of KIBRA on learning: among older adults the beneficial T-allele was positively associated with learning from feedback, but negatively with learning from observation. In younger adults, no effects of KIBRA were found. Our results add behavioral genetic evidence to emerging data showing age-related differences in how neural resources relate to memory functions, namely that hippocampal and striatal contributions to probabilistic category learning may vary with age. Such findings highlight the effects genetic factors can have on relative age-related decline of different memory functions.



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Scholar : These new articles for Atmospheric and Oceanic Science Letters are available online

The online platform for Taylor & Francis Online content New for Atmospheric and Oceanic Science Letters and online now on Taylor & Francis Online: Original Articles Future changes in precipitation extremes over China using the NEX-GDDP high-resolution daily downscaled data-set | Huo-Po Chen, Jian-Qi Sun & Hui-Xin Li Pages: 1-8 | DOI: 10.1080/16742834.2017.1367625 Free access to articles in this Editor's Choice collection from the Journal of Control and Decision. Don't miss it! To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

The evolution of human sleep: Technological and cultural innovation associated with sleep-wake regulation among Hadza hunter-gatherers

Publication date: December 2017
Source:Journal of Human Evolution, Volume 113
Author(s): David R. Samson, Alyssa N. Crittenden, Ibrahim A. Mabulla, Audax Z.P. Mabulla
Sleep is necessary for the survival of all mammalian life. In humans, recent investigations have generated critical data on the relationship between sleep and ecology in small-scale societies. Here, we report the technological and social strategies used to alter sleep environments and influence sleep duration and quality among a population of hunter-gatherers, the Hadza of Tanzania. Specifically, we investigated the effects that grass huts, sound levels, and fire had on sleep. We quantitatively compared thermal stress in outdoor environments to that found inside grass hut domiciles to test whether the huts function as thermoregulated microhabitats during the rainy season. Using physiological equivalent temperature (PET), we found that the grass huts provide sleep sites with less overall variation in thermal stress relative to outside baseline environments. We also investigated ambient acoustic measures of nighttime environments and found that sound significantly covaried with sleep-wake activity, with greater sound levels associating with less sleep. Finally, after controlling for ecological variables previously shown to influence sleep in this population, fire was shown to neither facilitate nor discourage sleep expression. Insofar as data among contemporary sub-tropical foragers can inform our understanding of past lifeways, we interpret our findings as suggesting that after the transition to full time terrestriality, it is likely that early Homo would have had novel opportunities to manipulate its environments in ways that could have significantly improved sleep quality. We further conclude that control over sleep environment would have been essential for migration to higher latitudes away from equatorial Africa.



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Editorial Board

Publication date: October 2017
Source:Journal of Human Evolution, Volume 111





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Rejuvenation of creep resistance of a Ni-base single-crystal superalloy by hot isostatic pressing

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Benjamin Ruttert, David Bürger, Lais Mujica Roncery, Alireza Basir Parsa, Philip Wollgramm, Gunther Eggeler, Werner Theisen
Ni-base single-crystal turbine blades are exposed to a combination of high temperatures and high stresses during their service life in high-pressure turbines of aero engines or stationary gas turbines. This unavoidably leads to various internal microstructural changes such as rafting and the formation of cavities. This study introduces a creep-rejuvenation-creep test cycle using one miniature Ni-base single-crystal creep specimen. A novel hot isostatic press providing high quenching rates was applied to rejuvenate the damaged microstructure of the specimen after the first high-temperature creep degradation before the same specimen was repeatedly creep-tested under the same initial creep conditions. After rejuvenating, microstructural results obtained from high-resolution microscopy prove that the creep cavities were closed, dislocation densities were re-set, and the original but now slightly finer γ/γ′-microstructure was restored without any recrystallization. The subsequent creep test of the rejuvenated specimen demonstrated that the proposed rejuvenation procedure in this work is a suitable method to reproduce the initial creep behavior and to thus prolong the lifetime of an already crept Ni-base single-crystal specimen.

Graphical abstract

http://ift.tt/2gK8BZC

Deformation analysis of gellan-gum based bone scaffold using on-the-fly tomography

Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Daniel Kytýř, Petr Zlámal, Petr Koudelka, Tomáš Fíla, Nela Krčmářová, Ivana Kumpová, Daniel Vavřík, Ana Gantar, Saša Novak
Porous hydrogel-based structures reinforced by bioactive nano-particles allows one to design scaffolds with controlled stiffness, strength, and permeability for bone-tissue engineering applications. To be able to reliably assess the mechanical properties, it is necessary to study the material's deformation response on a volumetric basis and in high detail. In this paper, we present an investigation on the compressive characteristics of highly-relaxing gellan-gum bioactive-glass scaffold subjected to continuous uniaxial quasi-static compression. The sample was compressed with a loading rate of 0.4 μm⋅s⁻¹ and simultaneously irradiated by X-rays during several micro-tomographical scans to obtain data for the evaluation of the deformation and strain fields using digital volume correlation (DVC). Such DVC evaluated on-the-fly micro-tomography was very challenging due to the low thickness of cell-walls and the material's intrinsic low attenuation of X-rays. Thus, we employed loading and tomographical devices equipped with a single-photon counting detector coupled with a DVC procedure, all developed in-house. From the acquired 34 tomographical scans, high-resolution voxel models with a resolution of 29.77 μm were developed and subjected to DVC to obtain detailed deformation and strain fields of the material. It is shown that the presented method is suitable for the precise determination of the deformation response of the predominantly organic material developed as a biocompatible, bioresorbable bone scaffold.

Graphical abstract

http://ift.tt/2gJzz3N

Ultrasonic-assisted soldering of fine-grained 7034 aluminum alloy using Sn-Zn solders below 300°C

Publication date: January 2018
Source:Ultrasonics Sonochemistry, Volume 40, Part A
Author(s): Weibing Guo, Tianmin Luan, Jingshan He, Jiuchun Yan
The fine-grained Al alloys prefer to be soldered at as low as temperature to keep their mechanical properties. Solders of Sn-4Zn, Sn-9Zn, and Sn-20Zn alloys were used to solder fine-grained 7034 Al alloy pieces by ultrasonic-assisted soldering below 300°C in air. The joint using Sn-4Zn solder had the highest tensile strength of 201MPa and the fractures occurred in both β-Sn and Sn-Zn eutectic phases. Such joint was much stronger than the 1060 Al joint using Sn-4Zn solder, and its strength had approached the strength of 7034 Al joint using Zn-5Al solder. The strength of the joints using Sn-9Zn and Sn-20Zn solders dropped to∼160MPa due to the appearance of weak interfaces between η-Zn and eutectic phases in the bond layers. All the joints using Sn-Zn solders had very strong interfacial bonding, and alumina interlayers were identified at all the interfaces. Al dissolved in the bond layer reacted with the O rapidly to form alumina interlayers at the interfaces under the ultrasonic action. Zn segregated at the interface and formed strong bonds with both the Al terminated surface of alumina and the bond layer, resulting in strong interfacial bonding between Sn-Zn solders and Al alloys.



http://ift.tt/2f02CfK

The effect of Zn incorporation on the optical band gap of CuGaS2: Ti thin films

Publication date: 1 January 2018
Source:Materials Letters, Volume 210
Author(s): Qingyan Li, Jiawei Wu, Yanlai Wang, Wenliang Fan, Jun Zhu, Xiaojing Wang, Ying Yang
A novel intermediate band (IB) material of Zn incorporation in Ti-doped CuGaS2 thin films has been successfully fabricated via a facile non vacuum method including ball milling, spin-coating and annealing. Experimental results have shown that the IB position of Ti-doped CuGaS2 thin films can be adjusted by Zn incorporation. In this study, the optical band gap has a shortening of 0.19eV when 0.6% Zn is added to the 1.5% Ti-doped CuGaS2. Due to the Zn addition, the grains grow larger, which is observable from the surface morphology of the thin films using scanning electron microscope (SEM). The energy dispersive X-ray analysis (EDAX) spectrum demonstrates that ball milling can effectively make Ti and Zn elements co-coped evenly into CuGaS2 thin films. Moreover, the improved optical property of the Ti-doped CuGaS2 thin films due to the Zn incorporation also sheds lights in developing new material that could be a potential light absorption layers candidate of high efficiency solar cells.



http://ift.tt/2gKrY4R

Glucose homeostasis in GHD children during long-term replacement therapy: a case−control study

Abstract

Purpose

To evaluate glucose homeostasis in children with growth hormone (GH) deficiency (GHD) receiving long-term replacement therapy.

Methods

We evaluated glucose, insulin, HOmeostasis Model Assessment (HOMA-IR), and HbA1c in 100 GHD children at diagnosis and during 5 years of therapy. One hundred healthy children comparable to patients were evaluated at baseline and after 1 and 5 years.

Results

No difference was detected at baseline between GHD patients and controls in glucose (79.58 ± 9.96 vs. 77.18 ± 8.20 mg/dl), insulin (4.50 ± 3.24 vs. 4.30 ± 2.60 µU/ml), HbA1c (5.20 ± 0.31 vs. 5.25 ± 0.33%) levels, and HOMA-IR (0.93 ± 0.72 vs. 0.86 ± 0.61). One year of GH was associated with a significant increase in insulin (7.21 ± 4.84, p < 0.001) and HOMA-IR (1.32 ± 0.98, p < 0.001) in GHD children, which became different from controls (p < 0.001 and p = 0.004). These parameters did not change further during the following years of treatment in GHD subjects. In contrast, controls did not show significant changes in insulin (4.40 ± 2.60) and HOMA-IR (0.82 ± 0.60) during the first year; however, at the fifth year of the study a significant increase in insulin (6.50 ± 3.50, p = 0.004) and HOMA-IR (1.29 ± 0.54, p < 0.001) was documented, making these parameters comparable between patients and controls.

Conclusions

Our results suggest that growth hormone (GH) treatment is not associated with significant impairment of insulin sensitivity in GHD children. The slight impairment observed in GHD adolescents after long-term GH is comparable to that physiologically occurring in healthy pubertal subjects.

http://ift.tt/2wCmuyx

PEGylation for enhancing nanoparticle diffusion in mucus

Publication date: Available online 4 September 2017
Source:Advanced Drug Delivery Reviews
Author(s): Justin T. Huckaby, Samuel K. Lai
The viscoelastic mucus secretions coating exposed organs such as the lung airways and the female reproductive tract can trap and quickly eliminate not only foreign pathogens and ultrafine particles but also particle-based drug delivery systems, thus limiting sustained and targeted drug delivery at mucosal surfaces. To improve particle distribution across the mucosa and enhance delivery to the underlying epithelium, many investigators have sought to develop nanoparticles capable of readily traversing mucus. The first synthetic nanoparticles shown capable of rapidly penetrating physiological mucus secretions utilized a dense coating of polyethylene glycol (PEG) covalently grafted onto the surface of preformed polymeric nanoparticles. In the decade since, PEG has become the gold standard in engineering mucus-penetrating drug carriers for sustained and targeted drug delivery to the lungs, gastrointestinal tract, eyes, and female reproductive tract. This review summarizes the history of the development of various PEG-based mucus-penetrating particles, and highlights the key physicochemical properties of PEG coatings and PEGylation strategies to achieve muco-inert PEG coatings on nanoparticle drug carriers for improved drug and gene delivery at mucosal surfaces.

Graphical abstract

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Editorial Board

Publication date: 1 July 2017
Source:Advanced Drug Delivery Reviews, Volume 116





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Preface: Molecular Mechanisms, Novel Modes of Regulation, and Therapeutic Strategies

Publication date: 1 July 2017
Source:Advanced Drug Delivery Reviews, Volume 116
Author(s): Guofeng You




http://ift.tt/2vFAE3c

α-Tubulin Acetylation Restricts Axon Overbranching by Dampening Microtubule Plus-End Dynamics in Neurons

Abstract

Axon growth is tightly controlled to establish functional neural circuits during brain development. Despite the belief that cytoskeletal dynamics is critical for cell morphology, how microtubule acetylation regulates axon development in the mammalian central nervous system remains unclear. Here, we report that loss of α-tubulin acetylation by ablation of MEC-17 in mice predisposes neurons to axon overbranching and overgrowth. Introduction of MEC-17^F183A lacking α-tubulin acetyltransferase activity into MEC-17-deficient neurons failed to rescue axon defects. Moreover, loss of α-tubulin acetylation led to increases in microtubule debundling, microtubule invasion into filopodia and growth cones, and microtubule plus-end dynamics along the axon. Taxol application dampened microtubule hyperdynamics and suppressed axon overbranching and overgrowth in MEC-17-deficient neurons. Thus, our study reveals that α-tubulin acetylation acts as a brake for axon overbranching and overgrowth by dampening microtubule dynamics, providing insight into the role of microtubule post-translational modifications in regulating neural development.

http://ift.tt/2gK0KeA

Development of Right-hemispheric Dominance of Inferior Parietal Lobule in Proprioceptive Illusion Task

Abstract

Functional lateralization can be an indicator of brain maturation. We have consistently shown that, in the adult brain, proprioceptive processing of muscle spindle afferents generating illusory movement of the right hand activates inferior frontoparietal cortical regions in a right-side dominant manner in addition to the cerebrocerebellar motor network. Here we provide novel evidence regarding the development of the right-dominant use of the inferior frontoparietal cortical regions in humans using this task. We studied brain activity using functional magnetic resonance imaging while 60 right-handed blindfolded healthy children (8–11 years), adolescents (12–15 years), and young adults (18–23 years) (20 per group) experienced the illusion. Adult-like right-dominant use of the inferior parietal lobule (IPL) was observed in adolescents, while children used the IPL bilaterally. In contrast, adult-like lateralized cerebrocerebellar motor activation patterns were already observable in children. The right-side dominance progresses during adolescence along with the suppression of the left-sided IPL activity that emerges during childhood. Therefore, the neuronal processing implemented in the adult's right IPL during the proprioceptive illusion task is likely mediated bilaterally during childhood, and then becomes right-lateralized during adolescence at a substantially later time than the lateralized use of the cerebrocerebellar motor system for kinesthetic processing.

http://ift.tt/2eZscS3

Arginine vasopressin improves the memory deficits in Han Chinese patients with first-episode schizophrenia

Publication date: Available online 5 September 2017
Source:Peptides
Author(s): Cai-Hong Geng, Chao Wang, Jun Yang, Hua Wang, Rui-Qing Ma, Xu Liu, Chang-Hong Wang
The memory impairment is a core deficit in the first-episode schizophrenia patients. Arginine vasopressin (AVP) in the brain can improve learning and memory. We performed multicentre, randomized, double-blind, placebo-controlled, parallel-group clinical trial to study the cognitive functioning in Han Chinese first-episode schizophrenic patients in a 12-week treatment regime with the intranasal administration of AVP (128 cases) or placebo (131 cases) in addition to the conventional treatment. The methods of positive and negative syndrome scale (PANSS), Wechsler memory scale-4th edition (WMS-IV) and event-related potential (ERP) were used to study the effects of AVP on the cognitive function. The results showed that (1) AVP concentration decreased in cerebrospinal fluid (CSF) of the right-handed Han Chinese first-episode schizophrenic patients comparing with that of the health volunteers (7.1±1.5pg/ml vs 13.3±1.9pg/ml, p<0.01), and did not change in plasma; (2) AVP significantly improved PANSS scores including total scores, positive symptoms, negative symptoms and general psychopathology comparing with those of the placebo group; (3) AVP elevated WMS-IV scores including the long-term memory (accumulation), short-term memory (recognition, comprehension), immediate memory (number recitation) and memory quotient 4, 8 and 12 weeks after treatment; and (4) AVP did not influence the latency and wave amplitude of target stimulus of P300 of right-handed Han Chinese first-episode schizophrenic patients. The data suggested that AVP might improve cognitive process, such as memorizing and extraction of the information although there were many changes of cognitive functions in the right-handed Han Chinese first-episode schizophrenic patients.



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Contribution of transcranial magnetic stimulation to assessment of brain connectivity and networks

Publication date: Available online 5 September 2017
Source:Clinical Neurophysiology
Author(s): Mark Hallett, Riccardo Di Iorio, Paolo Maria Rossini, Jung E Park, Robert Chen, Pablo Celnik, Antonio P. Strafella, Hideyuki Matsumoto, Yoshikazu Ugawa
The goal of this review is to show how transcranial magnetic stimulation (TMS) techniques can make a contribution to the study of brain networks. Brain networks are fundamental in understanding how the brain operates. Effects on remote areas can be directly observed or identified after a period of stimulation, and each section of this review will discuss one method. EEG analyzed following TMS is called TMS-evoked potentials (TEPs). A conditioning TMS can influence the effect of a test TMS given over the motor cortex. A disynaptic connection can be tested also by assessing the effect of a pre-conditioning stimulus on the conditioning-test pair. Basal ganglia-cortical relationships can be assessed using electrodes placed in the process of deep brain stimulation therapy. Cerebellar-cortical relationships can be determined using TMS over the cerebellum. Remote effects of TMS on the brain can be found as well using neuroimaging, including both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The methods complement each other since they give different views of brain networks, and it is often valuable to use more than one technique to achieve converging evidence. The final product of this type of work is to show how information is processed and transmitted in the brain.



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Pallidal low β-low γ phase-amplitude coupling inversely correlates with Parkinson disease symptoms

Publication date: Available online 5 September 2017
Source:Clinical Neurophysiology
Author(s): Christos Tsiokos, Mahsa Malekmohammadi, Nicholas Au Yong, Nader Pouratian
ObjectiveRecent discoveries suggest that it is most likely the coupling of β oscillations (13-30 Hz) and not merely their power that relates to Parkinson disease (PD) pathophysiology.MethodsWe analyzed power and phase amplitude coupling (PAC) in local field potentials (LFP) recorded from Pallidum after placement of deep brain stimulation (DBS) leads in nineteen PD patients and three patients with dystonia.ResultsWithin GPi, we identified PAC between phase of β and amplitude of high frequency oscillations (200-300 Hz) and distinct β-low γ (40-80 Hz) PAC both modulated by contralateral movement. Resting β-low γ PAC, also present in dystonia patients, inversely correlated with severity of rigidity and bradykinesia (R=-0.44, P=0.028). These findings were specific to the low β band, suggesting a differential role for the two β sub-bands.ConclusionsPAC is present across distinct frequency bands within the GPi. Given the presence of low β-low γ PAC in dystonia and the inverse correlation with symptom severity, we propose that this PAC may be a normal pallidal signal.SignificanceThis study provides new evidence on the pathophysiological contribution of local pallidal coupling and suggests similar and distinct patterns of coupling within GPi and STN in PD.



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The Associative Brain at Work: Evidence from Paired Associative Stimulation Studies in Humans

Publication date: Available online 5 September 2017
Source:Clinical Neurophysiology
Author(s): A. Suppa, A. Quartarone, H. Siebner, R. Chen, V. Di Lazzaro, P. Del Giudice, Walter Paulus, J.C. Rothwell, U. Ziemann, J. Classen
The original protocol of Paired Associative Stimulation (PAS) in humans implies repetitive cortical and peripheral nerve stimuli, delivered at specific inter-stimulus intervals, able to elicit non-invasively long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity in the human motor cortex. PAS has been designed to drive cortical LTP/LTD according to the Hebbian rule of associative plasticity. Over the last two decades, a growing number of researchers have increasingly used the PAS technique to assess cortical associative plasticity in healthy humans and in patients with movement disorders and other neuropsychiatric diseases. The present review covers the physiology, pharmacology, pathology and motor effects of PAS. Further sections of the review focus on new protocols of "modified PAS" and possible future application of PAS in neuromorphic circuits designed for brain-computer interface.



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Sea Buckthorn (Hippophaë rhamnoides L.) Oil Improves Atopic Dermatitis-Like Skin Lesions via Inhibition of NF-κB and STAT1 Activation

Background and Objectives: The objective of this study was to evaluate the topical effects of sea buckthorn (SBT) oil on atopic dermatitis (AD)-like lesions in a mouse model generated by repeated topical administration of DNCB in BALB/c mice. Methods: DNCB was applied repeatedly on the dorsal skin of mice to induce AD-like lesions. Following AD induction, SBT oil was applied daily on the dorsal skin for 4 weeks. The severity of skin lesions was examined macroscopically and histologically. We further measured the production of MDC/CCL22 and TARC/CCL17 in IFN-#x03B3;/TNF-α activated HaCaT cells. Results: Topically applied SBT oil in DNCB-treated mice ameliorated the severity score of dermatitis, decreased epidermal thickness, reduced spleen and lymph node weights, and prevented mast cell infiltration. In addition, SBT oil suppressed the Th2 chemokines TARC and MDC via dose-dependent inhibition of NF-#x03BA;B, JAK2/STAT1, and p38-MAPK signaling pathways in IFN-#x03B3;/TNF-α-activated HaCaT cells. Conclusion: These results suggest that SBT oil had a beneficial effect on AD-like skin lesions, partially via inhibition of the Th2 chemokines TARC and MDC in inflamed skin.
Skin Pharmacol Physiol 2017;30:268-276

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Cover Image, Volume 87, Issue 4

The cover image, by Tadej Battelino et al., is based on the Original Article Somapacitan, a once-weekly reversible albumin-binding GH derivative, in children with GH deficiency: A randomized dose-escalation trial, DOI: 10.1111/cen.13409.

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Increase in the circulating endocannabinoid 2-arachidonoylglycerol is associated with gabapentin use in septic ICU patients

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Glucose homeostasis in GHD children during long-term replacement therapy: a case−control study

Abstract

Purpose

To evaluate glucose homeostasis in children with growth hormone (GH) deficiency (GHD) receiving long-term replacement therapy.

Methods

We evaluated glucose, insulin, HOmeostasis Model Assessment (HOMA-IR), and HbA1c in 100 GHD children at diagnosis and during 5 years of therapy. One hundred healthy children comparable to patients were evaluated at baseline and after 1 and 5 years.

Results

No difference was detected at baseline between GHD patients and controls in glucose (79.58 ± 9.96 vs. 77.18 ± 8.20 mg/dl), insulin (4.50 ± 3.24 vs. 4.30 ± 2.60 µU/ml), HbA1c (5.20 ± 0.31 vs. 5.25 ± 0.33%) levels, and HOMA-IR (0.93 ± 0.72 vs. 0.86 ± 0.61). One year of GH was associated with a significant increase in insulin (7.21 ± 4.84, p < 0.001) and HOMA-IR (1.32 ± 0.98, p < 0.001) in GHD children, which became different from controls (p < 0.001 and p = 0.004). These parameters did not change further during the following years of treatment in GHD subjects. In contrast, controls did not show significant changes in insulin (4.40 ± 2.60) and HOMA-IR (0.82 ± 0.60) during the first year; however, at the fifth year of the study a significant increase in insulin (6.50 ± 3.50, p = 0.004) and HOMA-IR (1.29 ± 0.54, p < 0.001) was documented, making these parameters comparable between patients and controls.

Conclusions

Our results suggest that growth hormone (GH) treatment is not associated with significant impairment of insulin sensitivity in GHD children. The slight impairment observed in GHD adolescents after long-term GH is comparable to that physiologically occurring in healthy pubertal subjects.

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Pseudomembranous changes in the dermis: a novel observation and potential clue for evolving lipodermatosclerosis?

ABSTRACT

Lipodermatosclerosis (LDS) is a well-recognized form of fibrosing panniculitis. Although chronic cases are readily diagnosed, early and evolving lesions may be clinically mistaken for cellulitis and other forms of panniculitis. Most pathologists are familiar with a pseudomembranous type of fat necrosis as a useful feature of chronic LDS. Although non-specific, this distinctive pattern of fat necrosis helps in supporting a diagnosis of LDS in the appropriate clinical context. The histopathologic features of early and evolving LDS and those involving the dermis are less well documented. We report a case of early LDS showing extensive pseudomembranous changes in the dermis on a superficial skin biopsy where progression to a classic established lesion was documented clinically. We suspect that this previously unreported and unusual finding may be a histopathologic clue for evolving lesions of LDS.

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Evaluation and comparison of staining patterns of factor XIIIa (AC-1A1), adipophilin, and GATA3 in sebaceous neoplasia

Abstract

Introduction

Reliable nuclear immunohistochemical stains for sebaceous neoplasms have not been readily available. Positive nuclear staining has been reported by GATA3 and factor XIIIa (AC-1A1). We sought to determine the diagnostic utility of these nuclear stains by comparing their staining pattern to adipophilin, a consistently positive cytoplasmic stain.

Methods

Cases with the diagnosis of sebaceous hyperplasia, sebaceous adenoma, sebaceous epithelioma/sebaceoma, and sebaceous carcinoma, nonsebaceous neoplasms (basal cell carcinoma, and squamous cell carcinoma) were examined. Intensity and extent of staining of the basal cells and mature sebocytes were evaluated for each stain.

Results

Factor XIIIa (AC-1A1) was 87.3% sensitive for all sebaceous neoplasms and 95.1% specific and demonstrated high inter-observer reliability. Adipophilin was 83.2% sensitive and 87.8% specific. GATA3 was the least sensitive (80.9%) and specific (75.6%) marker. When factor XIIIa was compared against composite staining of all three markers its staining was still uniquely significant (p = 0.0210).

Conclusion

Factor XIIIa (AC-1A1) is a sensitive and specific nuclear marker for sebaceous differentiation. Its diagnostic utility exceeds that of adipophilin. Factor XIIIa should be included in the expanding group of immunohistochemical and special stains which can be utilized to aid in the diagnosis of sebaceous neoplasms.

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Imported Fire Ant Envenomation: A Clinicopathologic Study of a Recognizable Form of Arthropod Assault Reaction

Background

Skin reactions to the sting of the imported fire ant have characteristic clinicopathological features.

Methods

One case of experimental envenomation was prospectively followed during 48 hours, with biopsies. In addition, six cases from our laboratory were retrospectively evaluated histopathologically for the following features: spongiosis, exocytosis (and type of cells), pustule formation, erosion/ulceration, epidermal necrosis, scale/crust, papillary dermal edema, inflammatory dermal infiltrate (cell type, density, depth, distribution, shape), red blood cell extravasation, vasculopathy, vasculitis.

Results

The typical lesion follows a very distinctive clinical and histopathologic evolution over 48 hours, with the formation of a subepidermal pustule overlying a wedge shaped area of dermal collagen basophilic degeneration with scattered neutrophils. In the six cases retrieved from our files, the main features were a superficial and deep dermal, perivascular, periadnexal and interstitial infiltrate consisting of neutrophils, with basophilic degeneration of the collagen. A subepidermal pustule was noted in half of the cases.

Conclusions

In biopsies taken in a clinical setting, even in the absence of the characteristic subepidermal pustule, the diagnosis of imported fire ant sting can be suspected if there is a superficial and deep perivascular, periadnexal and interstitial infiltrate composed of neutrophils, with some basophilic denaturation of collagen.

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Scholar : These new articles for Voice and Speech Review are available online

The online platform for Taylor & Francis Online content New for Voice and Speech Review and online now on Taylor & Francis Online: Forum Vocal traditions: Lessac Kinesensics Marth Munro, Deborah Kinghorn, Barry Kur, Robin Aronson, Nancy Krebs & Sean Turner Pages: 1-13 | DOI: 10.1080/23268263.2017.1370834 Original Articles Bridging the gap between classical and contemporary vocal technique: implications for the choral rehearsal Brian J. Winnie Pages: 1-17 | DOI: 10.1080/23268263.2017.1370803 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Increase in the circulating endocannabinoid 2-arachidonoylglycerol is associated with gabapentin use in septic ICU patients

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Scholar : These new articles for Transport are available online

The online platform for Taylor & Francis Online content New for Transport and online now on Taylor & Francis Online: Original Articles Analysis of impact of meteorological conditions on human factors in estimating the risk of railway accidents Dejan Aleksić, Milan Marković, Marko Vasiljević, Gordan Stojić, Norbert Pavlović & Ilija Tanackov Pages: 1-14 | DOI: 10.3846/16484142.2017.1332684 Wheel–rail wear investigation on a heavy haul balloon loop track through simulations of slow speed wagon dynamics Yan Quan Sun, Maksym Spiryagin, Colin Cole & Dwayne Nielsen Pages: 1-10 | DOI: 10.3846/16484142.2017.1355843 Off-street parking facility location on urban transportation network considering multiple objectives: a case study of Isfahan (Iran) Mahdi Eskandari & Ali Shahandeh Nookabadi Pages: 1-12 | DOI: 10.3846/16484142.2017.1345004 Congestion effects of autonomous taxi fleets Michal Maciejewski & Joschka Bischoff Pages: 1-10 | DOI: 10.3846/16484142.2017.1347827 Ship mooring to jetties under the crosscurrent Vytautas Paulauskas, Donatas Paulauskas, Birutė Plačienė & Raimondas Barzdžiukas Pages: 1-7 | DOI: 10.3846/16484142.2017.1354069 Ground-borne noise and vibration transmitted from subway networks to multi-storey reinforced concrete buildings Konstantinos Vogiatzis & Harris Mouzakis Pages: 1-8 | DOI: 10.3846/16484142.2017.1347895 Identifying dominant stakeholder perspectives on urban freight policies: a Q-analysis on urban consolidation centres in the Netherlands | Ron van Duin, Marijn Slabbekoorn, Lori Tavasszy & Hans Quak Pages: 1-14 | DOI: 10.3846/16484142.2017.1350996 Pattern recognition based speed forecasting methodology for urban traffic network Tamás Tettamanti, Alfréd Csikós, Krisztián Balázs Kis, Zsolt János Viharos & István Varga Pages: 1-12 | DOI: 10.3846/16484142.2017.1352027 Condition monitoring of railway track systems by using acceleration signals on wheelset axle-boxes Andrzej Chudzikiewicz , Roman Bogacz , Mariusz Kostrzewski & Robert Konowrocki Pages: 1-12 | DOI: 10.3846/16484142.2017.1342101 Different urban consolidation centre scenarios: impact on external costs of last-mile deliveries Marko Veličković, Đurđica Stojanović, Svetlana Nikoličić & Marinko Maslarić Pages: 1-11 | DOI: 10.3846/16484142.2017.1350995 Determining the impact of directionality on road markings retroreflectivity using dynamic method Dario Babić, Anđelko Ščukanec & Darko Babić Pages: 1-9 | DOI: 10.3846/16484142.2017.1339208 Analysis of different visual strategies of 'isolated vehicle' and 'disturbed vehicle' Nicola Bongiorno, Gaetano Bosurgi, Orazio Pellegrino & Giuseppe Sollazzo Pages: 1-8 | DOI: 10.3846/16484142.2017.1343750 Free access to articles in this Editor's Choice collection from the Journal of Control and Decision. Don't miss it! To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Prognostic and Predictive Biomarkers in Breast Cancer: Past, Present and Future

Publication date: Available online 4 September 2017
Source:Seminars in Cancer Biology
Author(s): Andrea Nicolini, Paola Ferrari, Michael J. Duffy
Following a diagnosis of breast cancer, the most immediate challenges in patient management are the determination of prognosis and identification of the most appropriate adjuvant systemic therapy. Determining prognosis can best be addressed with a combination of traditional clinicopathological prognostic factors, biomarkers such as HER2/neu and specific multigene genes tests. Amongst the best validated prognostic multigene tests are uPA/PAI1, Oncotype DX and MammaPrint. Oncotype DX and MammaPrint, may be used for predicting outcome and aiding adjunct therapy decision making in patients with ER-positive, HER2-negative breast cancers that are either lymph node-negative or node positive (1-3 metastatic nodes), while uPA/PAI-1 may be similarly used in ER-positive, lymph node-negative patients. For selecting likely response to endocrine therapy, both estrogen receptors (ER) and progesterone receptors (PR) should be measured. On the other hand, for identifying likely response to anti-HER2 therapy, determination of HER2 gene amplification or overexpression is necessary. To identify new prognostic and predictive biomarkers for breast cancer, current research is focusing on tumor and circulating DNA (ctDNA) and RNA (e.g., micro RNAs) and circulating tumor cells. A promising ctDNA biomarker is the mutational status of ER (ESR1) for predicting the emergence of resistance to aromatase inhibitors. Challenges for future research include the identification of biomarkers for predicting response to radiotherapy and specific forms of chemotherapy.



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Deciding on Active Surveillance or Surgery for Primary Management of Low Risk Papillary Thyroid Cancer

Condition:   Thyroid Cancer Stage I
Intervention:  
Sponsors:   University Health Network, Toronto;   Ontario Ministry of Health and Long Term Care;   Canadian Cancer Society Research Institute (CCSRI)
Recruiting - verified August 2017

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Breathing-motion-compensated robotic guided stereotactic body radiation therapy

Abstract

Purpose

We retrospectively evaluated the patterns of failure for robotic guided real-time breathing-motion-compensated (BMC) stereotactic body radiation therapy (SBRT) in the treatment of tumors in moving organs.

Patients and methods

Between 2011 and 2016, a total of 198 patients with 280 lung, liver, and abdominal tumors were treated with BMC-SBRT. The median gross tumor volume (GTV) was 12.3 cc (0.1–372.0 cc). Medians of mean GTV BED_{α/β =10  Gy} (BED = biological effective dose) was 148.5 Gy₁₀ (31.5–233.3 Gy₁₀) and prescribed planning target volume (PTV) BED_{α/β =10  Gy} was 89.7 Gy₁₀ (28.8–151.2 Gy₁₀), respectively. We analyzed overall survival (OS) and local control (LC) based on various factors, including BEDs with α/β ratios of 15 Gy (lung metastases), 21 Gy (primary lung tumors), and 27 Gy (liver metastases).

Results

Median follow-up was 10.4 months (2.0–59.0 months). The 2‑year actuarial LC was 100 and 86.4% for primary early and advanced stage lung tumors, respectively, 100% for lung metastases, 82.2% for liver metastases, and 90% for extrapulmonary extrahepatic metastases. The 2‑year OS rate was 47.9% for all patients. In uni- and multivariate analysis, comparatively lower PTV prescription dose (equivalence of 3 × 12–13 Gy) and higher average GTV dose (equivalence of 3 × 18 Gy) to current practice were significantly associated with LC. For OS, Karnofsky performance score (100%), gender (female), and SBRT without simultaneous chemotherapy were significant prognostic factors. Grade 3 side effects were rare (0.5%).

Conclusions

Robotic guided BMC-SBRT can be considered a safe and effective treatment for solid tumors in moving organs. To reach sufficient local control rates, high average GTV doses are necessary. Further prospective studies are warranted to evaluate these points.

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Downregulated expression of miR-223 promotes Toll-like receptor-activated inflammatory responses in macrophages by targeting RhoB

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Ningjie Zhang, Liyao Fu, Yanhong Bu, Yao Yao, Yongjun Wang
Toll-like receptors (TLRs) induced-inflammatory response must be tightly regulated to avoid impairment in host itself. Numerous factors have been identified in regulation of TLR-triggered inflammatory response. Among these, microRNAs (miRNAs) are small non-coding RNA molecules which have got much attention. MiR-223, which highly expresses in myeloid cells of the bone marrow, has reported to participate in kinds of inflammatory responses by targeting inflammasome sensor-NLRP3 to repress production of IL-6 and IL-1β, and thus attenuate inflammatory response. However, the function of miR-223 in TLRs-activated inflammatory response of macrophages is not clear. Here we found miR-223 expression is dramatically reduced in macrophages by TLR ligand stimulation (e.g. LPS, CpG and poly (I:C)). The down-regulated miR-223 leads to the increase in the RhoB expression, which induce the activation of NF-κB and MAPK signaling, promoting TNF-α, IL-6 and IL-1β production upon LPS stimulation. In addition, the histone deacetylase inhibitor trichostatin A increased miR-223 expression obviously in TLR-triggered macrophages, which in turn suppressed RhoB expression and downstream IL-6 production, suggesting that the inhibition of miR-223 by histone deacetylation may be involved in the regulation of TLR-activated inflammatory response. Herein, our findings suggest that miR-223-RhoB axis might be a novel target for the treatment of inflammatory diseases.



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Sex and the elderly: Attitudes to long-lived women and men in early Anglo-Saxon England

Publication date: December 2017
Source:Journal of Anthropological Archaeology, Volume 48
Author(s): Christine M. Cave, Marc F. Oxenham
Currently, in the industrialised world, women have a higher life expectancy than men, a pattern often seen in the past as well. However, in Britain, from the Neolithic to medieval period, it has been suggested that men outlived women. One issue with such statistics is that age estimation techniques are often biased, underestimating the age of older individuals, while the oldest individuals in a sample often disappear into catch-all categories such as 50+ years. Here we employ an approach that renders visible the older individuals in three archaeological cemeteries (Great Chesterford; Mill Hill; Worthy Park) to assess gendered longevity and differential mortuary treatment of the elderly in Anglo-Saxon England. We find that women tended to outlive men and while some elderly females were respected in death, others were more likely to receive a non-normative burial than males. Old males tended to receive 'elaborate' burial, and were less likely to receive a deviant burial. It appears that ageing in Anglo-Saxon England was a gendered process, with some older women respected like their male counterparts, while others were possibly perceived less auspiciously.



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