Ιατρικά Άρθρα: 12/28/17

Πέμπτη 28 Δεκεμβρίου 2017

A novel bivalent fusion vaccine induces broad immunoprotection against Staphylococcus aureus infection in different murine models

Publication date: Available online 28 December 2017
Source:Clinical Immunology
Author(s): Liuyang Yang, Heng Zhou, Ping Cheng, Yun Yang, Yanan Tong, Qianfei Zuo, Jiao Luo, Qiang Feng, Quanming Zou, Hao Zeng
With more and more drug-resistant Staphylococcus aureus strains emerging in hospitals, there is an urgent need to develop an effective vaccine to combat S. aureus infection. In this study, we constructed a novel bivalent fusion vaccine, SpA-DKKAA-FnBPA37-507 (SF), based on the D domain of staphylococcal protein A (SpA) and the A domain of fibronectin-binding protein A (FnBPA). Immunisation with SF induced a more ideal protective effect compared with the single components alone in a sepsis model. It also showed broad immunoprotection against seven FnBPA isotypes. Vaccination with SF induced strong antibodies responses and Th1/Th17 polarized cellular responses. Further we demonstrated the protective effect of antibodies by the opsonophagocytic assay (OPA) and passive immunisation. Moreover, vaccination with SF showed protective efficacy in a murine pneumonia model and skin abscess model. These results suggest that SF can be regarded as a promising vaccine candidate for the prevention of S. aureus infections.

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Emotion dysregulation and smoking among treatment-seeking smokers

Publication date: April 2018
Source:Addictive Behaviors, Volume 79
Author(s): Andrew H. Rogers, Jafar Bakhshaie, Andres G. Viana, Kara Manning, Nubia A. Mayorga, Lorra Garey, Amanda M. Raines, Norman B. Schmidt, Michael J. Zvolensky
IntroductionThere has been increased scholarly interest in advancing the study of emotion dysregulation and substance use. However, there is limited study of emotion dysregulation in the context of smoking. The current study examined the emotion dysregulation global construct and sub facets in relation to negative affect reduction expectancies, coping motives, perceived barriers for quitting, and the severity of problems experienced during quit attempts.MethodTreatment seeking smokers (n=469; 48.2% female, Mage=36.59, SD=13.58) enrolled in a smoking cessation trial and completed baseline measures of smoking cognitions and emotion dysregulation.ResultsResults indicated that the emotion dysregulation global score was significantly associated with each of the smoking dependent variables. Additionally, difficulty accessing emotion regulation strategies and difficulty engaging in goal-directed behavior were significantly associated with the dependent variables.ConclusionOverall, this is the first study to evaluate relations between multidimensional facets of emotion dysregulation and clinically relevant smoking variables. Emotion dysregulation may be an important treatment target for changing smoking.

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Trauma exposure and heavy drinking and drug use among college students: Identifying the roles of negative and positive affect lability in a daily diary study

Publication date: April 2018
Source:Addictive Behaviors, Volume 79
Author(s): Nicole H. Weiss, Krysten W. Bold, Ateka A. Contractor, Tami P. Sullivan, Stephen Armeli, Howard Tennen
Trauma exposure is linked to heavy drinking and drug use among college students. Extant research reveals positive associations between negative affect lability and both trauma exposure and alcohol use. This study aimed to extend past research by using daily diary methods to test whether (a) individuals with (versus without) trauma exposure experience greater negative and positive affect lability, (b) negative and positive affect lability are associated with heavy drinking and drug use, and (c) negative and positive affect lability mediate the relations between trauma exposure and heavy drinking and drug use. Participants were 1640 college students (M age=19.2, 54% female, 80% European American) who provided daily diary data for 30days via online surveys. Daily diaries assessed negative and positive affect and substance use (i.e., percent days of heavy drinking, percent days of drug use, total number of drugs used). Individuals with (versus without) a history of trauma exposure demonstrated higher levels of negative and positive affect lability. Negative, but not positive, affect lability was associated with percent days of heavy drinking, percent days of drug use, and total number of drugs used, and mediated the associations between trauma exposure and heavy drinking and drug use outcomes. Findings provide support for the underlying role of negative affect lability in the relations between trauma exposure and heavy drinking and drug use among college students, suggesting that treatments targeting negative affect lability may potentially serve to reduce heavy drinking and drug use among trauma-exposed college students.

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Identity as a cannabis user is related to problematic patterns of consumption among emerging adults

Publication date: April 2018
Source:Addictive Behaviors, Volume 79
Author(s): Claire E. Blevins, Ana M. Abrantes, Bradley J. Anderson, Celeste M. Caviness, Debra S. Herman, Michael D. Stein
IntroductionCannabis use has become a more normative, socially-acceptable behavior in the United States, despite research indicating that frequent use may become problematic for some individuals. Emerging adulthood, a time of identity development, is the most common time for cannabis use. Cannabis self-concept, or one's identification with cannabis as part of their personality or identity, is one factor that may influence use behavior. This study extends previous research that reported a link between self-concept, motivational factors, and normative beliefs by evaluating relationships between cannabis self-concept, motives for use, motivation to change, perceived descriptive norms, as well as cannabis-related outcomes (use, using alone, and cannabis-related problems).MethodsEmerging adults who used cannabis in the previous month (n=345, 53.9% male, mean age 21.0, 67.5% Non-Latino White) were recruited from a community sample for a health behaviors study. Participants were assessed for explicit cannabis self-concept, frequency of use, problems associated with use, motives for use, motivation to change, and normative beliefs about others' use.ResultsParticipants reported using cannabis on an average of 17.9 (SD=11.1) days of the previous month. Correlational analyses revealed that cannabis self-concept was positively associated with frequency of use, use-related problems, several motives for use, descriptive norms, and with using cannabis alone. Multivariate analyses revealed that rates of use, problems, and social and enhancement motives were independently and positively associated (p<0.05) with cannabis self-concept, while self-concept was negatively associated with desire to reduce cannabis use.ConclusionsCannabis self-concept may be a marker for more problematic patterns of use.

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Effects of alcohol and cigarette use on the initiation, reinitiation, and persistence of cannabis use from adolescence to emerging adulthood

Publication date: April 2018
Source:Addictive Behaviors, Volume 79
Author(s): Sanjana Pampati, Anne Buu, Yi-Han Hu, Carlos F. Mendes de Leon, Hsien-Chang Lin
ObjectiveAdolescent cannabis use has been associated with several negative outcomes. A previous study on an adult sample found alcohol and cigarette use to be associated with three cannabis use stages: initiation, reinitiation, and persistence, which represent distinct periods of use regarding progression and severity. Yet, the risk factors associated with these important stages have never been examined in a longitudinal study spanning adolescence to emerging adulthood.MethodsUsing longitudinal data from Add Health Waves 1–3, 1775 nonusers, 200 prior users, and 384 current users of cannabis were identified who were at risk of cannabis use initiation, reinitiation, and persistence, respectively. Three logistic regressions were conducted to examine the effects of prior cigarette and alcohol use on the three cannabis use stages, controlling for sociodemographic factors.ResultsEarly onset of cigarette use (OR=2.04, p=0.006) and higher alcohol use frequency (OR=1.40, p<0.001) were associated with cannabis use initiation. Greater cigarette use quantity was associated with a lower likelihood of reinitiation of cannabis use (OR=0.58, p=0.02). Increased cannabis use frequency (OR=1.72, p=0.006) and higher alcohol use frequency (OR=1.32, p=0.048) were associated with persistence of cannabis use. Sociodemographic factors such as household income, sex, and being older adolescents were associated with different cannabis use stages.ConclusionsPrior cigarette and alcohol use affect the risk of initiation, reinitiation, and persistence of cannabis use. The specific risk factors vary across different cannabis use stages. Interventions to prevent adolescent cannabis use should recognize these different risk factors and tailor to the stages of cannabis use.

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Editorial Board and Contents

Publication date: January 2018
Source:Trends in Immunology, Volume 39, Issue 1

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Play It Again, SAM: Macrophages Control Peripheral Fat Metabolism

Publication date: Available online 28 December 2017
Source:Trends in Immunology
Author(s): Kevin A. Guttenplan, Shane A. Liddelow
Macrophages and other immune cells are increasingly recognized to have unique and nontraditional functions in various tissues of the body. In a recent issue of Nature Medicine, Pirzgalska et al. [1] characterized a unique set of tissue-specialized macrophages that modulate the connection between the nervous system and subcutaneous fat.

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Reishi mushroom Ganoderma lucidum Modulates IgA production and alpha-defensin expression in the rat small intestine

Publication date: 25 March 2018
Source:Journal of Ethnopharmacology, Volume 214
Author(s): Atsuhito Kubota, Masaki Kobayashi, Sota Sarashina, Reiko Takeno, Keisuke Okamoto, Katsuya Narumi, Ayako Furugen, Yuji Suzuki, Natsuko Takahashi, Ken Iseki
Ethnopharmacological relevanceImmunoglobulin A (IgA) secretion and alpha-defensins play a role in the innate immune system to protect against infection. Ganoderma lucidum (W.Curt.: Fr.) P. Karst. (Reishi) is a well-known mushroom in traditional Chinese medicine. This study aimed to determine the effects of Reishi on IgA secretion from Peyer's patch (PP) cells and alpha-defensin-5 (RD-5) and RD-6 expression in the rat small intestine.Materials and methodsThe rats received an oral injection of 0.5–5mg/kg of Reishi powder (1mL/kg) by sonde. All animals were euthanized 24h after Reishi administration. We examined RD-5, RD-6, and Toll-like receptor (TLR) 4 mRNA levels in the jejunum, ileum, and in Peyer's patches (PP) through quantitative real-time PCR analysis. IgA secretion from PP was measured through enzyme-linked immunosorbent assay of the supernatant after primary culture.ResultsReishi increased IgA secretion in the presence of lipopolysaccharide (LPS) and increased TLR4 mRNA levels, but had no effect on the viability of PP cells. Moreover, Reishi increased RD-5, RD-6, and TLR4 mRNA levels significantly in the ileum in a concentration-dependent manner.ConclusionsReishi can induce IgA secretion and increase the mRNA levels of RD-5 and RD-6 in the rat small intestine, through a TLR4-dependent pathway. The present results indicate that Reishi might reduce the risk of intestinal infection.

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METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m6A Modification

Publication date: Available online 28 December 2017
Source:Cell Stem Cell
Author(s): Hengyou Weng, Huilin Huang, Huizhe Wu, Xi Qin, Boxuan Simen Zhao, Lei Dong, Hailing Shi, Jennifer Skibbe, Chao Shen, Chao Hu, Yue Sheng, Yungui Wang, Mark Wunderlich, Bin Zhang, Louis C. Dore, Rui Su, Xiaolan Deng, Kyle Ferchen, Chenying Li, Miao Sun, Zhike Lu, Xi Jiang, Guido Marcucci, James C. Mulloy, Jianhua Yang, Zhijian Qian, Minjie Wei, Chuan He, Jianjun Chen
N⁶-methyladenosine (m⁶A), the most prevalent internal modification in eukaryotic messenger RNAs (mRNAs), plays critical roles in many bioprocesses. However, its functions in normal and malignant hematopoiesis remain elusive. Here, we report that METTL14, a key component of the m⁶A methyltransferase complex, is highly expressed in normal hematopoietic stem/progenitor cells (HSPCs) and acute myeloid leukemia (AML) cells carrying t(11q23), t(15;17), or t(8;21) and is downregulated during myeloid differentiation. Silencing of METTL14 promotes terminal myeloid differentiation of normal HSPCs and AML cells and inhibits AML cell survival/proliferation. METTL14 is required for development and maintenance of AML and self-renewal of leukemia stem/initiation cells (LSCs/LICs). Mechanistically, METTL14 exerts its oncogenic role by regulating its mRNA targets (e.g., MYB and MYC) through m⁶A modification, while the protein itself is negatively regulated by SPI1. Collectively, our results reveal the SPI1-METTL14-MYB/MYC signaling axis in myelopoiesis and leukemogenesis and highlight the critical roles of METTL14 and m⁶A modification in normal and malignant hematopoiesis.

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The role of N⁶-methyladenosine (m⁶A) modification in normal and malignant hematopoiesis remains elusive. Weng et al. report the essential role of METTL14, a key component of the m⁶A methyltransferase complex, in self-renewal and differentiation of hematopoietic/leukemic stem cells and reveal the SPI1-METTL14-MYB/MYC signaling axis in myelopoiesis and leukemogenesis.

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Reconstruction of the Human Colon Epithelium In Vivo

Publication date: Available online 28 December 2017
Source:Cell Stem Cell
Author(s): Shinya Sugimoto, Yuki Ohta, Masayuki Fujii, Mami Matano, Mariko Shimokawa, Kosaku Nanki, Shoichi Date, Shingo Nishikori, Yoshihiro Nakazato, Tetsuya Nakamura, Takanori Kanai, Toshiro Sato
Genetic lineage tracing has revealed that Lgr5⁺ murine colon stem cells (CoSCs) rapidly proliferate at the crypt bottom. However, the spatiotemporal dynamics of human CoSCs in vivo have remained experimentally intractable. Here we established an orthotopic xenograft system for normal human colon organoids, enabling stable reconstruction of the human colon epithelium in vivo. Xenografted organoids were prone to displacement by the remaining murine crypts, and this could be overcome by complete removal of the mouse epithelium. Xenografted organoids formed crypt structures distinctively different from surrounding mouse crypts, reflecting their human origin. Lineage tracing using CRISPR-Cas9 to engineer an LGR5-CreER knockin allele demonstrated self-renewal and multipotency of LGR5⁺ CoSCs. In contrast to the rapidly cycling properties of mouse Lgr5⁺ CoSCs, human LGR5⁺ CoSCs were slow-cycling in vivo. This organoid-based orthotopic xenograft model enables investigation of the functional behaviors of human CoSCs in vivo, with potential therapeutic applications in regenerative medicine.

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Sugimoto et al. established an orthotopic xenotransplantation system for human normal colon organoids. Using LGR5-CreER knockin organoids for genetic lineage tracing, they demonstrated the self-renewal and multipotency of LGR5⁺ colon stem cells in mouse colon. Interestingly, human LGR5⁺ colon stem cells showed slower cycling than those of mice in vivo.

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METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m6A Modification

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Reconstruction of the Human Colon Epithelium In Vivo

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Synthesis, characterization, and mechanical and dynamic mechanical studies of β-alanine trimer-grafted SBR

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Yihong Zhao, Lin Fu, Li Jia
Two β-alanine trimer-grafted SBRs with varied grafting densities, 3a and 3b, have been synthesized. The grafting density of 3b is about twice of that of 3a. FT-IR and DSC evidences suggest that the β-alanine trimer segments in both 3a and 3b exist exclusively in the β-sheet secondary structure, and the β-sheets stack to form crystals in the continuous SBR phase. The Tm of the β-sheet crystals in 3b is higher than the Tm of those in 3a. This likely suggests that the size of the crystals is somewhat larger in 3b than in 3a. TEM revealed that the β-sheet crystals are rod-like, with lengths on the order of a few tens of nanometers and widths of a few nanometers. The aspect ratio is much lower than that of the β-sheet crystals in segmented TPEs. The most prominent difference in the tensile behavior between 3a and 3b is strain hardening. The former is devoid of strain hardening, while the latter displays strong strain hardening. Overall, the high β-alanine content in 3b leads to improvement of stiffness, ultimate strength and overall toughness at the sacrifice of extensibility and elastic recovery compared to 3a. Dynamic mechanical studies showed that both 3a and 3b display very low loss factors, typical for TPEs with monodisperse hard segments that form β-sheet crystals, at temperatures up to 105 °C.

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Nanomaterials at the neural interface

Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50
Author(s): Denis Scaini, Laura Ballerini
Interfacing the nervous system with devices able to efficiently record or modulate the electrical activity of neuronal cells represents the underlying foundation of future theranostic applications in neurology and of current openings in neuroscience research. These devices, usually sensing cell activity via microelectrodes, should be characterized by safe working conditions in the biological milieu together with a well-controlled operation-life. The stable device/neuronal electrical coupling at the interface requires tight interactions between the electrode surface and the cell membrane. This neuro-electrode hybrid represents the hyphen between the soft nature of neural tissue, generating electrical signals via ion motions, and the rigid realm of microelectronics and medical devices, dealing with electrons in motion. Efficient integration of these entities is essential for monitoring, analyzing and controlling neuronal signaling but poses significant technological challenges. Improving the cell/electrode interaction and thus the interface performance requires novel engineering of (nano)materials: tuning at the nanoscale electrode's properties may lead to engineer interfacing probes that better camouflaged with their biological target. In this brief review, we highlight the most recent concepts in nanotechnologies and nanomaterials that might help reducing the mismatch between tissue and electrode, focusing on the device's mechanical properties and its biological integration with the tissue.

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Local versus landscape-scale effects of anthropogenic land-use on forest species richness

Publication date: January 2018
Source:Acta Oecologica, Volume 86
Author(s): G. Buffa, S. Del Vecchio, E. Fantinato, V. Milano
The study investigated the effects of human-induced landscape patterns on species richness in forests. For 80 plots of fixed size, we measured human disturbance (categorized as urban/industrial and agricultural land areas), at 'local' and 'landscape' scale (500 m and 2500 m radius from each plot, respectively), the distance from the forest edge, and the size and shape of the woody patch. By using GLM, we analyzed the effects of disturbance and patch-based measures on both total species richness and the richness of a group of specialist species (i.e. the 'ancient forest species'), representing more specific forest features. Patterns of local species richness were sensitive to the structure and composition of the surrounding landscape. Among the landscape components taken into account, urban/industrial land areas turned out as the most threatening factor for both total species richness and the richness of the ancient forest species. However, the best models evidenced a different intensity of the response to the same disturbance category as well as a different pool of significant variables for the two groups of species. The use of groups of species, such as the ancient forest species pool, that are functionally related and have similar ecological requirements, may represent an effective solution for monitoring forest dynamics under the effects of external factors. The approach of relating local assessment of species richness, and in particular of the ancient forest species pool, to land-use patterns may play an important role for the science-policy interface by supporting and strengthening conservation and regional planning decision making.

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Complex foraging ecology of the red harvester ant and its effect on the soil seed bank

Publication date: January 2018
Source:Acta Oecologica, Volume 86
Author(s): Pedro Luna, Juan Héctor García-Chávez, Wesley Dáttilo
Granivory is an important interaction in the arid and semi-arid zones of the world, since seeds form an abundant and nutritious resource in these areas. While species of the genus Pogonomyrmex have been studied in detail as seed predators, their impact on seed abundance in the soil has not yet been explored in sufficient depth. We studied the impact of the harvesting activities of the ant Pogonomyrmex barbatus on seed abundance in the soil of the Zapotitlán valley, Mexico. We found that P. barbatus activity significantly impacts the abundance of seeds in the soil, which is lower in the sites where P. barbatus forages than it is in sites with no recorded foraging. We also found that P. barbatus distributes intact seeds of three tree species, two of which are nurse plants, and could consequently be promoting the establishment of these species. Using tools derived from graph theory, we observed that the ant-seed interactions exhibit a nested pattern; where more depredated seed species seem to be the more spatially abundant in the environment. This study illustrates the complex foraging ecology of the harvester ant P. barbatus and elucidates its effect on the soil seed bank in a semi-arid environment.

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Elevated native terrestrial snail abundance and diversity in association with an understory shrub, Berberis thunbergii, in a North American deciduous forest

Publication date: January 2018
Source:Acta Oecologica, Volume 86
Author(s): Ryan M. Utz, Timothy A. Pearce, Danielle L. Lewis, Joseph C. Mannino
Invasive terrestrial plants often substantially reshape environments, yet how such invasions affect terrestrial snail assemblages remains understudied. We investigated how snail assemblages in deciduous forest soils with dense Berberis thunbergii (Japanese barberry), an invasive shrub in eastern North America, differ from forest areas lacking the shrub. Leaf litter and soil samples were collected from forest patches with dense B. thunbergii understories and adjacent control areas within two exurban forest tracts in western Pennsylvania, U.S.A. Snails were identified to species and quantified by standard diversity metrics. Contrary to our expectations, snails were significantly more abundant and diverse in B. thunbergii-invaded areas. Despite differences in abundance, the snail community composition did not differ between invaded and control habitats. The terrestrial snail assemblage we observed, which was composed entirely of native species, appears to respond favorably to B. thunbergii invasion and therefore may not be negatively impacted by physicochemical changes to soils typically observed in association with the plant. Such findings could reflect the fact that B. thunbergii likely creates more favorable habitat for snails by creating cooler, more humid, and more alkaline soil environments. However, the snail assemblages we retrieved may consist mostly of species with high tolerance to environmental degradation due to a legacy of land use change and acid deposition in the region.

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Effect of Cu and Zn ion-exchange locations on mordenite performance in dimethyl ether carbonylation

Publication date: June 2018
Source:Microporous and Mesoporous Materials, Volume 263
Author(s): Allen A.C. Reule, Vinay Prasad, Natalia Semagina
Cu²⁺ and Zn²⁺ ion-exchange locations in mordenite (MOR) were evaluated using infrared spectroscopy, pore-size distribution, and temperature-programmed reduction. Isolated copper ions were the most abundant ion-exchanged species, as detected by UV-vis spectroscopy, in addition to oxide nanoparticles, with no presence of binuclear species, which was assigned to a low copper loading of 0.3 Cu/Al. The characterization revealed that only zinc could exchange in 8-membered rings. Hartree-Fock modeling confirmed copper exchange into 12-membered rings involving at least one T1 atom, and zinc exchange in T4 sites and in 8-membered structures, including T3 sites. Copper ion exchange did not offer improvement in the dimethyl ether carbonylation rate or selectivity over acidic mordenite. Zinc ion exchange led to the selectivity and stability improvement with some loss of activity. This work contributes to the understanding of acid and metal site contribution to DME carbonylation and contributes to the understanding for Cu²⁺ and Zn²⁺ ion-exchange locations in MOR with a low metal/Al loading (<0.2).

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Towards a better understanding of long-term wood-chemistry variations in old-growth forests: A case study on ancient Pinus uncinata trees from the Pyrenees

Publication date: 1 June 2018
Source:Science of The Total Environment, Volume 625
Author(s): Andrea Hevia, Raúl Sánchez-Salguero, J. Julio Camarero, Allan Buras, Gabriel Sangüesa-Barreda, J. Diego Galván, Emilia Gutiérrez
Dendrochemical studies in old forests are still underdeveloped. Old trees growing in remote high-elevation areas far from direct human influence constitute a promising biological proxy for the long-term reconstructions of environmental changes using tree-rings. Furthermore, centennial-long chronologies of multi-elemental chemistry at inter- and intra-annual resolution are scarce. Here, we use a novel non-destructive method by applying Micro X-ray fluorescence (μXRF) to wood samples of old Pinus uncinata trees from two Pyrenean high-elevation forests growing on acidic and basic soils. To disentangle ontogenetic (changes in tree age and diameter) from environmental influences (e.g., climate warming) we compared element patterns in sapwood (SW) and heartwood (HW) during the pre-industrial (1700–1849) and industrial (1850–2008) periods. We quantified tree-ring growth, wood density and relative element concentrations at annual (TRW, tree-ring) to seasonal resolution (EW, earlywood; LW, latewood) and related them to climate variables (temperature and precipitation) and volcanic eruptions in the 18th and 19th centuries. We detected differences for most studied elements between SW and HW along the stem and also between EW and LW within rings. Long-term positive and negative trends were observed for Ca and K, respectively. Cl, P and S showed positive trends during the industrial period. However, differences between sites were also notable. Higher values of Mg, Al, Si and the Ca/Mn ratio were observed at the site with acidic soil. Growing-season temperatures were positively related to growth, maximum wood density and to the concentration of most elements. Peaks in S, Fe, Cl, Zn and Ca were linked to major volcanic eruptions (e.g., Tambora in 1815). Our results reveal the potential of long-term wood-chemistry studies based on the μXRF non-destructive technique to reconstruct environmental changes.

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Toxicity of the readily leachable fraction of urban PM2.5 to human lung epithelial cells: Role of soluble metals

Publication date: April 2018
Source:Chemosphere, Volume 196
Author(s): Simonetta Palleschi, Barbara Rossi, Giovanna Armiento, Maria Rita Montereali, Elisa Nardi, Simona Mazziotti Tagliani, Marco Inglessis, Antonio Gianfagna, Leopoldo Silvestroni
Fine airborne particulate matter (PM2.5) has been repeatedly associated with adverse health effects in humans. The PM2.5 soluble fraction, and soluble metals in particular, are thought to cause lung damage. Literature data, however, are not consistent and the role of leachable metals is still under debate. In this study, Winter and Summer urban PM2.5 aqueous extracts, obtained by using a bio-compatible solution and different contact times at 37 °C, were used to investigate cytotoxic effects of PM2.5 in cultured lung epithelial cells (A549) and the role played by the leachable metals Cu, Fe, Zn, Ni, Pb and Cd. Cell viability and migration, as well as intracellular glutathione, extracellular cysteine, cysteinylglycine and homocysteine concentrations, were evaluated in cells challenged with both PM2.5 extracts before and after ultrafiltration and artificial metal ion solutions mimicking the metal composition of the genuine extracts. The thiol oxidative potential was also evaluated by an abiotic test. Results demonstrate that PM2.5 bioactive components were released within minutes of PM2.5 interaction with the leaching solution. Among these are i) low MW (<3 kDa) solutes inducing oxidative stress and ii) high MW and/or water-insoluble compounds largely contributing to thiol oxidation and to increased homocysteine levels in the cell medium. Cu and/or Ni ions likely contributed to the effects of Summer PM2.5 extracts. Nonetheless, the strong bio-reactivity of Winter PM2.5 extracts could not be explained by the presence of the studied metals. A possible role for PM2.5 water-extractable organic components is discussed.

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Blood derivatives awaken in regenerative medicine strategies to modulate wound healing

Publication date: Available online 28 December 2017
Source:Advanced Drug Delivery Reviews
Author(s): Bárbara B. Mendes, Manuel Gómez-Florit, Pedro S. Babo, Rui L. Reis, Rui M.A. Domingues, Manuela E. Gomes
Blood components play key roles in the modulation of the wound healing process and, together with the provisional fibrin matrix ability to selectively bind bioactive molecules and control its spatial-temporal presentation, define the complex microenvironment that characterize this biological process. As a biomimetic approach, the use of blood derivatives in regenerative strategies has awaken as a source of multiple therapeutic biomolecules. Nevertheless, and despite their clinical relevance, blood derivatives have been showing inconsistent therapeutic results due to several factors, including proper control over their delivery mechanisms. Herein, we highlight recent trends on the use biomaterials to protect, sequester and deliver these pools of biomolecules in tissue engineering and regenerative medicine approaches. Particular emphasis is given to strategies that enable to control their spatiotemporal delivery and improve the selectivity of presentation profiles of the biomolecules derived from blood derivatives rich in platelets. Finally, we discussed possible directions for biomaterials design to potentiate the aimed regenerative effects of blood derivatives and achieve efficient therapies.

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Founder mutation in IKBKAP gene causes vestibular impairment in familial dysautonomia

Publication date: February 2018
Source:Clinical Neurophysiology, Volume 129, Issue 2
Author(s): Joel V. Gutiérrez, Horacio Kaufmann, Jose-Alberto Palma, Carlos Mendoza-Santiesteban, Vaughan G. Macefield, Lucy Norcliffe-Kaufmann
ObjectiveTo assess vestibular function in patients with familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy – caused by a mutation in the IKBKAP gene (c.2204 + 6 T>C) – and characterized by marked gait ataxia.MethodsCervical and vestibular evoked myogenic potentials (cVEMPs and oVEMPs) were recorded from the sternocleidomastoid (SCM) and extraocular muscles in 14 homozygous patients, 2 heterozygous patients, and 15 healthy controls during percussion of the forehead.ResultscVEMP and oVEMP amplitudes were significantly lower, and peak latencies significantly delayed, in the FD patients. There were no differences in overall EMG during attempted maximal voluntary contractions of the SCM muscle, suggesting intact efferent function. The two heterozygotes with a minor haplotype missense (R696P) mutation in exon 19 of the IKBKAP gene had cVEMP responses less affected than the homozygous.ConclusionsThe founder mutation in the IKBKAP gene affects the development of vestibular afferent pathways, leading to attenuated cVEMPs.SignificanceVestibular abnormalities may contribute to the gait ataxia in FD.

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Interhemispheric motor interactions in hemiparetic children with perinatal stroke: Clinical correlates and effects of neuromodulation therapy

Publication date: February 2018
Source:Clinical Neurophysiology, Volume 129, Issue 2
Author(s): Derek Eng, Ephrem Zewdie, Patrick Ciechanski, Omar Damji, Adam Kirton
ObjectiveBrain stimulation and constraint therapy may enhance function after perinatal stroke but mechanisms are unknown. We characterized interhemispheric interactions (IHI) in hemiparetic children and explored their relationship to motor function and neuromodulation.MethodsForty-five hemiparetic perinatal stroke subjects aged 6–19 years completed a clinical trial of repetitive-transcranial magnetic stimulation (rTMS) and constraint therapy. Paired-pulse TMS measured IHI in cases and normal controls. Suprathreshold conditioning stimuli preceded contralateral test stimuli bidirectionally: stroke to non-stroke (SNS) and non-stroke to stroke (NSS). Primary outcome was the interhemispheric ratio (IHR) between conditioned and test only MEP amplitudes X100 (<100 implied inhibition). Motor outcomes at baseline and post-intervention were compared to IHR.ResultsProcedures were well tolerated. IHI occurred bidirectionally in controls. Eighteen stroke participants had complete data. IHR were increased in stroke participants in both directions. SNS IHR was >100 (facilitation) in 39% of measurements and correlated with better motor function. NSS IHR correlated with poorer motor function. Intervention-induced clinical change was not associated with IHR.ConclusionsInterhemispheric interactions are altered and related to clinical function, but not necessarily neuromodulation, in children with perinatal stroke.SignificanceAdding interhemispheric interactions to evolving models of developmental plasticity following early injury may advance neuromodulation strategies.

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Editorial Board

Publication date: January 2018
Source:Journal of Anxiety Disorders, Volume 53

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Publisher Acknowledgement

Publication date: January 2018
Source:Journal of Anxiety Disorders, Volume 53

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Gut Microbes Egested during Bites of Infected Sand Flies Augment Severity of Leishmaniasis via Inflammasome-Derived IL-1β

Publication date: Available online 28 December 2017
Source:Cell Host & Microbe
Author(s): Ranadhir Dey, Amritanshu B. Joshi, Fabiano Oliveira, Lais Pereira, Anderson B. Guimarães-Costa, Tiago D. Serafim, Waldionê de Castro, Iliano V. Coutinho-Abreu, Parna Bhattacharya, Shannon Townsend, Hamide Aslan, Alec Perkins, Subir Karmakar, Nevien Ismail, Morgan Karetnick, Claudio Meneses, Robert Duncan, Hira L. Nakhasi, Jesus G. Valenzuela, Shaden Kamhawi
Leishmania donovani parasites are the cause of visceral leishmaniasis and are transmitted by bites from phlebotomine sand flies. A prominent feature of vector-transmitted Leishmania is the persistence of neutrophils at bite sites, where they protect captured parasites, leading to enhanced disease. Here, we demonstrate that gut microbes from the sand fly are egested into host skin alongside Leishmania parasites. The egested microbes trigger the inflammasome, leading to a rapid production of interleukin-1β (IL-1β), which sustains neutrophil infiltration. Reducing midgut microbiota by pretreatment of Leishmania-infected sand flies with antibiotics or neutralizing the effect of IL-1β in bitten mice abrogates neutrophil recruitment. These early events are associated with impairment of parasite visceralization, indicating that both gut microbiota and IL-1β are important for the establishment of Leishmania infections. Considering that arthropods harbor a rich microbiota, its potential egestion after bites may be a shared mechanism that contributes to severity of vector-borne disease.

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Teaser

Neutrophils recruited to sand fly bite sites shelter Leishmania, augmenting disease. Dey et al. demonstrate that egestion of sand fly gut microbes into host skin primes the inflammasome to produce IL-1β, which sustains neutrophil recruitment. Removing gut microbiota or blocking IL-1β before transmission abolishes neutrophil recruitment and impairs Leishmania dissemination.

http://ift.tt/2ldVK1t

Leukotriene B4-Mediated Neutrophil Recruitment Causes Pulmonary Capillaritis during Lethal Fungal Sepsis

Publication date: Available online 28 December 2017
Source:Cell Host & Microbe
Author(s): Esther K.S. Lee, Mark R. Gillrie, Lu Li, Jason W. Arnason, Jung Hwan Kim, Liane Babes, Yuefei Lou, Amir Sanati-Nezhad, Stephen K. Kyei, Margaret M. Kelly, Christopher H. Mody, May Ho, Bryan G. Yipp
Candida albicans bloodstream infection causes fungal septicaemia and death in over half of afflicted patients. Polymorphonuclear leukocytes (PMN) mediate defense against invasive candidiasis, but their role in protection versus tissue injury and sepsis is unclear. We observe PMN intravascular swarming and subsequent clustering in response to C. albicans yeast in a lethal septic mouse and human pulmonary circulation model. Live C. albicans sequester to the endothelium and are immediately captured by complement-dependent PMN chemotaxis, which is required for host survival. However, complement activation also leads to Leukotriene B4 (LTB4)-mediated intravascular PMN clustering and occlusion, resulting in capillaritis with pulmonary hemorrhage and hypoxemia. This clustering is unique to fungi and triggered by fungal cell wall components. PMN clustering is absent in mice lacking LTB4-receptor, and capillaritis is attenuated upon pharmacological LTB4 blockade without affecting phagocytosis. Therefore, therapeutically disrupting infection-induced capillaritis may limit organ injury without impairing host defense during fungal sepsis.

Graphical abstract

Teaser

Fungal sepsis has a high mortality rate. Using live imaging, Lee, et al. discovered that the lung bloodstream is an important site of host defense; however, fungi caused extensive vessel occlusions due to leukotriene-meditated neutrophil capillaritis. Inhibiting occlusion improved lung function and outcomes, thus revealing a therapeutic target.

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Bacteria Facilitate Enteric Virus Co-infection of Mammalian Cells and Promote Genetic Recombination

Publication date: Available online 28 December 2017
Source:Cell Host & Microbe
Author(s): Andrea K. Erickson, Palmy R. Jesudhasan, Melinda J. Mayer, Arjan Narbad, Sebastian E. Winter, Julie K. Pfeiffer
RNA viruses exist in genetically diverse populations due to high levels of mutations, many of which reduce viral fitness. Interestingly, intestinal bacteria can promote infection of several mammalian enteric RNA viruses, but the mechanisms and consequences are unclear. We screened a panel of 41 bacterial strains as a platform to determine how different bacteria impact infection of poliovirus, a model enteric virus. Most bacterial strains, including those extracted from cecal contents of mice, bound poliovirus, with each bacterium binding multiple virions. Certain bacterial strains increased viral co-infection of mammalian cells even at a low virus-to-host cell ratio. Bacteria-mediated viral co-infection correlated with bacterial adherence to cells. Importantly, bacterial strains that induced viral co-infection facilitated genetic recombination between two different viruses, thereby removing deleterious mutations and restoring viral fitness. Thus, bacteria-virus interactions may increase viral fitness through viral recombination at initial sites of infection, potentially limiting abortive infections.

Graphical abstract

Teaser

Enteric viruses rely on intestinal bacteria for replication and transmission. By screening a diverse panel of bacterial strains, Erickson et al. demonstrate that bacteria differentially bind poliovirus and that some bacterial strains promote viral co-infection and genetic recombination, thus enhancing viral fitness.

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Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer's disease

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Giacomo Koch, Sonia Bonnì, Maria Concetta Pellicciari, Elias P. Casula, Matteo Mancini, Romina Esposito, Viviana Ponzo, Silvia Picazio, Francesco Di Lorenzo, Laura Serra, Caterina Motta, Michele Maiella, Camillo Marra, Mara Cercignani, Alessandro Martorana, Carlo Caltagirone, Marco Bozzali
Memory loss is one of the first symptoms of typical Alzheimer's disease (AD), for which there are no effective therapies available. The precuneus (PC) has been recently emphasized as a key area for the memory impairment observed in early AD, likely due to disconnection mechanisms within large-scale networks such as the default mode network (DMN). Using a multimodal approach we investigated in a two-week, randomized, sham-controlled, double-blinded trial the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the PC on cognition, as measured by the Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite in 14 patients with early AD (7 females). TMS combined with electroencephalography (TMS-EEG) was used to detect changes in brain connectivity. We found that rTMS of the PC induced a selective improvement in episodic memory, but not in other cognitive domains. Analysis of TMS-EEG signal revealed an increase of neural activity in patients' PC, an enhancement of brain oscillations in the beta band and a modification of functional connections between the PC and medial frontal areas within the DMN.Our findings show that high-frequency rTMS of the PC is a promising, non-invasive treatment for memory dysfunction in patients at early stages of AD. This clinical improvement is accompanied by modulation of brain connectivity, consistently with the pathophysiological model of brain disconnection in AD.

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Serotonergic and cholinergic modulation of functional brain connectivity: A comparison between young and older adults

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Bernadet L. Klaassens, Joop M.A. van Gerven, Erica S. Klaassen, Jeroen van der Grond, Serge A.R.B. Rombouts
Aging is accompanied by changes in neurotransmission. To advance our understanding of how aging modifies specific neural circuitries, we examined serotonergic and cholinergic stimulation with resting state functional magnetic resonance imaging (RS-fMRI) in young and older adults. The instant response to the selective serotonin reuptake inhibitor citalopram (30 mg) and the acetylcholinesterase inhibitor galantamine (8 mg) was measured in 12 young and 17 older volunteers during a randomized, double blind, placebo-controlled, crossover study. A powerful dataset consisting of 522 RS-fMRI scans was obtained by acquiring multiple scans per subject before and after drug administration. Group × treatment interaction effects on voxelwise connectivity with ten functional networks were investigated (p < .05, FWE-corrected) using a non-parametric multivariate analysis technique with cerebrospinal fluid, white matter, heart rate and baseline measurements as covariates. Both groups showed a decrease in sensorimotor network connectivity after citalopram administration. The comparable findings after citalopram intake are possibly due to relatively similar serotonergic systems in the young and older subjects. Galantamine altered connectivity between the occipital visual network and regions that are implicated in learning and memory in the young subjects. The lack of a cholinergic response in the elderly might relate to the well-known association between cognitive and cholinergic deterioration at older age.

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High Annual Hospital Volume is Associated with Decreased in Hospital Mortality and Complication Rates Following Treatment of Abdominal Aortic Aneurysms: Secondary Data Analysis of the Nationwide German DRG Statistics from 2005 to 2013

Publication date: Available online 27 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Matthias Trenner, Andreas Kuehnl, Michael Salvermoser, Benedikt Reutersberg, Sarah Geisbuesch, Volker Schmid, Hans-Henning Eckstein
ObjectivesThe aim of this study was to analyse the association between annual hospital procedural volume and post-operative outcomes following repair of abdominal aortic aneurysms (AAA) in Germany.MethodsData were extracted from nationwide Diagnosis Related Group (DRG) statistics provided by the German Federal Statistical Office. Cases with a diagnosis of AAA (ICD-10 GM I71.3, I71.4) and procedure codes for endovascular aortic repair (EVAR; OPS 5–38a.1*) or open aortic repair (OAR; OPS 5–38.45, 5–38.47) treated between 2005 and 2013 were included. Hospitals were empirically grouped to quartiles depending on the overall annual volume of AAA procedures. A multilevel multivariable regression model was applied to adjust for sex, medical risk, type of procedure, and type of admission. Primary outcome was in hospital mortality. Secondary outcomes were complications, use of blood products, and length of stay (LOS). The association between AAA volume and in hospital mortality was also estimated as a function of continuous volume.ResultsA total of 96,426 cases, of which 11,795 (12.6%) presented as ruptured (r)AAA, were treated in >700 hospitals (annual median: 501). The crude in hospital mortality was 3.3% after intact (i)AAA repair (OAR 5.3%; EVAR 1.7%). Volume was inversely associated with mortality after OAR and EVAR. Complication rates, LOS, and use of blood products were lower in high volume hospitals. After rAAA repair, crude mortality was 40.4% (OAR 43.2%; EVAR 27.4%). An inverse association between mortality and volume was shown for rAAA repair; the same accounts for the use of blood products. When considering volume as a continuous variate, an annual caseload of 75–100 elective cases was associated with the lowest mortality risk.ConclusionsIn hospital mortality and complication rates following AAA repair are inversely associated with annual hospital volume. The use of blood products and the LOS are lower in high volume hospitals. A minimum annual case threshold for AAA procedures might improve post-operative results.

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Feasibility Study of a Novel Thoraco-abdominal Aortic Hybrid Device (SPIDER-graft) in a Translational Pig Model

Publication date: Available online 28 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Eike S. Debus, Tilo Kölbel, Anna Duprée, Günter Daum, Harleen L. Sandhu, Daniel Manzoni, Sabine H. Wipper
BackgroundThe hybrid SPIDER-graft consists of a proximal descending aortic stent graft and a conventional six branched Dacron graft for open abdominal aortic repair. Technical feasibility with regard to avoiding thoracotomy and extracorporeal circulation (ECC) during thoraco-abdominal aortic hybrid repair and peri-procedural safety of this novel device are unknown.Material and methodsThis was a feasibility and safety study in domestic pigs (75–85 kg). The abdominal aorta including iliac bifurcation, left renal artery, and visceral arteries were exposed via retroperitoneal access. The right iliac branch was first temporarily anastomosed end to side to the distal aorta via partial clamping. During inflow reduction and infra-coeliac cross-clamping, the coeliac trunk (CT) was divided and the proximal stent graft portion of the SPIDER-graft was deployed into the descending aorta via the CT ostium. Retrograde visceral and antegrade aorto-iliac blood flow was maintained via the iliac side branch. The visceral, renal, and iliac arteries were sequentially anastomosed, finally replacing the first iliac end to side anastomosis. Technical success, blood flow, periods of ischaemia, and peri-procedural complications were evaluated after intra-operative completion angiography and post-operative computed tomography angiography.ResultsSix animals underwent successful thoracic stent graft deployment and distal open reconstruction without peri-operative death. The median thoracic graft implantation time was 4.5 min, and the median ischaemia times before reperfusion were 10 min for the CT, 8 min for the superior mesenteric artery, 13 min for the right renal artery, and 22 min for the left renal artery. Angiography demonstrated appropriate graft implantation and blood flow measurements confirmed sufficient blood flow through all side branches.ConclusionIn this translational pig model, thoraco-abdominal hybrid repair using the novel SPIDER-graft was successful in avoiding thoracotomy and ECC. Technical feasibility and safety appear promising, but need to be reassessed in humans.

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CONTRIBUTION OF PHOTODYNAMIC THERAPY IN WOUND HEALING: A SYSTEMATIC REVIEW

Publication date: Available online 28 December 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Vanessa Nesi-Reis, Daniele Stéfanie Sara Lopes Lera-Nonose, Jully Oyama, Marielle Priscila Paula Silva-Lalucci, Izabel Galhardo Demarchi, Sandra Mara Alessi Aristides, Jorge Juarez Vieira Teixeira, Thaís Gomes Verzignassi Silveira, Maria Valdrinez Campana Lonardoni
ObjectiveWe researched articles that used photodynamic therapy (PDT) in skin wound healing in humans.MethodsThe systematic review was conducted throughout scientific articles that investigated the action of PDT on wound healing in humans, published from July 2005 to March 2017, in the data bases PubMed and LILACS.ResultsThe main types of wound described in selected articles in this review were chronic ulcer, non-melanoma skin cancer. For accomplishing the PDT, second generation of photosensitizing agents with laser or light emitting diode were used. The studies demonstrated that PDT contribute in several ways to the wound healing process: leading to cellular death; reducing or increasing inflammation; stimulating fibroblasts proliferation and, consequently, of collagen and elastin; raising transforming growth factor beta and metalloproteinases. Based on this, PDT provided good results in wound healing process, acting in several steps and accelerating tissue repair.ConclusionsPDT improved healing in many wound models in humans, revealing itself as a promising therapeutic modality, stimulating wound healing and remodelling.

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Longitudinal Serum and Urine Steroid Metabolite Profiling in a 46,XY Infant with Prenatally Identified POR Deficiency

Publication date: Available online 28 December 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Hiroyuki Ono, Chikahiko Numakura, Keiko Homma, Tomonobu Hasegawa, Seiji Tsutsumi, Fumiko Kato, Yasuko Fujisawa, Maki Fukami, Tsutomu Ogata
Although POR deficiency (PORD) is assumed to be accompanied by excessive placental androgen accumulation and enhanced adrenal and testicular androgen production via the backdoor pathway as well as compromised testicular androgen production via the frontdoor pathway, there is no direct evidence for the flux of excessive placental androgens into the fetal circulation and for the production of dihydrotestosterone (DHT) via the backdoor pathway. We examined longitudinal serum and urine steroid metabolite profiles in a 46,XY infant with PORD who was prenatally identified because of the progressive fetal masculinization and maternal virilization from the mid-gestation and the presence of fetal radio-humeral synostosis and was confirmed to have compound heterozygous mutations of POR (p.Q201X and p.R457H). The results showed (1) markedly and inappropriately elevated serum androstenedione and testosterone (T) values at birth, (2) a markedly increased serum DHT value with a normal DHT/T ratio at birth, (3) transient elevation of serum T and DHT values accompanied by a normal DHT/T ratio and concomitant elevations of intermediate steroid metabolites on both the frontdoor and backdoor pathways at 30 days of age, and (4) persistent PORD-compatible urine steroid profiles. Although the data obtained from a single infantile patient are too premature to be generalized, they imply: (1) the transfer of excessive placental androgens into the fetal as well as the maternal circulations from the mid-gestation, (2) lack of a clinically discernible amount of DHT production via the adrenal backdoor pathway around birth, and (3) the activation of both the frontdoor and backdoor pathways in the testis around the mini-puberty, with no production of a clinically discernible amount of DHT via the testicular backdoor pathway.

Graphical abstract

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Duplicated membrane estrogen receptors in the European sea bass (Dicentrarchus labrax): phylogeny, expression and regulation throughout the reproductive cycle

Publication date: Available online 28 December 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Patrícia I.S. Pinto, André R. Andrade, M. Dulce Estêvão, M. Victoria Alvarado, Alicia Felip, Deborah M. Power
The numerous estrogen functions reported across vertebrates have been classically explained by their binding to specific transcription factors, the nuclear estrogen receptors (ERs). Rapid non-genomic estrogenic responses have also been recently identified in vertebrates including fish, which can be mediated by membrane receptors such as the G protein-coupled estrogen receptor (Gper). In this study, two genes for Gper, namely gpera and gperb, were identified in the genome of a teleost fish, the European sea bass. Phylogenetic analysis indicated they were most likely retained after the 3R teleost-specific whole genome duplication and raises questions about their function in male and female sea bass. Gpera expression was mainly restricted to brain and pituitary in both sexes while gperb had a widespread tissue distribution with higher expression levels in gill filaments, kidney and head kidney. Both receptors were detected in the hypothalamus and pituitary of both sexes and significant changes in gpers expression were observed throughout the annual reproductive season. In female pituitaries, gpera showed an overall increase in expression throughout the reproductive season while gperb levels remained constant. In the hypothalamus, gpera had a higher expression during vitellogenesis and decreased in fish entering the ovary maturation and ovulation stage, while gperb expression increased at the final atresia stage. In males, gpers expression was constant in the hypothalamus and pituitary throughout the reproductive cycle apart from the mid- to late testicular development stage when a significant up-regulation of gpera occurred in the pituitary. The differential sex, seasonal and subtype-specific expression patterns detected for the two novel gper genes in sea bass suggests they may have acquired different and/or complementary roles in mediating estrogens actions in fish, namely on the neuroendocrine control of reproduction.

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Value of external carotid artery resistive index for diagnosis of cavernous sinus dural arteriovenous fistula and determination of malignant type

Publication date: May–June 2018
Source:Clinical Imaging, Volume 49
Author(s): Chai Kobkitsuksakul, Wasawat Soratcha, Ekachat Chanthanaphak
PurposeCavernous sinus dural arteriovenous fistula (CSDAVF) causes hemodynamic disturbance in the arteries, which is detected by carotid Doppler sonography (CDS). The objective of the study was designed for validation of CDS in the diagnosis of CSDAVF.Material and methods42 CSDAVF patients confirmed by angiography were enrolled. All patients were performed CDS before angiography. Evaluations of CDS parameters were compared with control subjects.ResultsThe ECA resistive index (RI) shows the best performance. The highest yield shown on left ECA RI and increased from 78.6% to 91.7% on malignant-typed.ConclusionCDS may be beneficial as the screening tool for CSDAVF.

Graphical abstract

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The lateral habenula interacts with the hypothalamo-pituitary adrenal axis response upon stressful cognitive demand in rats

Publication date: 2 April 2018
Source:Behavioural Brain Research, Volume 341
Author(s): Victor Mathis, Brigitte Cosquer, Alexandra Barbelivien, Karine Herbeaux, Béatrice Bothorel, Dominique Sage-Ciocca, Vincent-Joseph Poirel, Chantal Mathis, Lucas Lecourtier
The lateral habenula (LHb) is involved in emotional and cognitive behaviors. Recently, we have shown in rats that blockade of excitatory inputs to the LHb not only induced deficits of memory retrieval in the water maze, but also altered swim strategies (i.e., induced excessive thigmotaxis). The latter observation, although consistent with the occurrence of memory deficits, could also possibly be the consequence of an excessive level of stress, further suggesting a role for the LHb in the stress response in our behavioral paradigm. To test this hypothesis we performed in rats intra-LHb infusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 267 ng/side in 0.3 μL), or vehicle, and assessed the responsiveness of the hypothalamo-pituitary adrenal (HPA) axis to environmental stressful or non-stressful situations. We have measured plasma corticosterone (CORT) concentrations at different time points before and following intra-LHb infusion of CNQX – or of the same volume of vehicle – in three conditions: during the probe test of a water maze experiment; in an anxiety test, the elevated plus maze; and in a home cage condition. Whereas there were no differences in the home cage condition and in the elevated plus maze, in the water maze experiment we observed that CNQX-treated rats presented, along with memory deficits, a higher level of blood CORT than vehicle-treated rats. These results suggest that perturbations of the modulation of the HPA axis are consecutive to the alteration of LHb function, whether it is the result of a defective direct control of the LHb over the HPA axis, or the consequence of memory deficits.

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Individual differences in incentive salience attribution are not related to suboptimal choice in rats

Publication date: 2 April 2018
Source:Behavioural Brain Research, Volume 341
Author(s): Paulina López, Rodrigo Alba, Vladimir Orduña
Previous research has shown great variation in the extent to which individual rats attribute incentive salience to stimuli that are predictors of reinforcement. When using the Pavlovian Conditioned Approach procedure, in which a discrete stimulus is presented contingently before the delivery of reinforcement, the attribution of incentive salience is demonstrated by sign-tracking behavior (responses directed toward the stimulus predictor of reinforcement), while an absence of this attribution is reflected by goal-tracking behavior (responses directed toward the source of reinforcement). It has been reported that sign-tracking subjects have a higher tendency to perform some maladaptive behaviors than goal-tracking subjects, and that in non-classified rats, increasing the incentive salience of the stimuli promotes suboptimal choice in the "suboptimal choice procedure". In this task, subjects are presented with two alternatives, one of them better in terms of the information provided by the discriminative stimuli, but worse in terms of probability of reinforcement (suboptimal alternative). Integrating these ideas, we hypothesized that sign-trackers would behave suboptimally, in contrast to goal-trackers. In the present study, 45 rats were classified according to their performance in the Pavlovian Conditioned Approach procedure and subjects with extreme values (sign-trackers, and goal-trackers) were evaluated in the suboptimal choice procedure. Both groups were found to behave optimally, with no differences between them. The difference between groups in capacity of attribution of incentive salience was preserved during the entire experiment, suggesting that this variable is not related to choice performance in the suboptimal choice procedure.

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Failure of further validation for survival nomograms in oropharyngeal cancer: issues and challenges

Publication date: Available online 28 December 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Paolo Bossi, Rosalba Miceli, Roberta Granata, Simona Naimo, Gabriele Infante, Laura Deborah Locati, Nicola Alessandro Iacovelli, Carlo Fallai, Lisa Licitra, Ester Orlandi
The two nomograms recently validated as prognostic tools for patients with oropharyngeal cancer treated with curative radiation-based therapy, identify social and educational level as significant predictors of survival outcome. We retrospectively tested these nomograms in 184 consecutive subjects treated from April 2004 to January 2016. Complete information regarding disease, survival status, and nomograms covariates were retrieved for 174 patients, with a median follow-up of 51 months. Calibration of the nomograms was obtained by evaluating the ability to accurately predict the absolute risk level; discriminative ability estimated by the Harrell C statistic was tested by assessing the ability of the nomograms to rank the patients from low risk to high risk.The outcome predicted by the nomograms was worse than observed, especially for progression-free survival. This may be due to several factors: geographic and genetic background, smoke, alcohol use, the different national health system organization, which provides universal and free-of-charge coverage to all individuals and the setting of treatment in clinical practice, outside of clinical trials. Our results show that the usefulness of nomograms to predict outcome of oropharyngeal cancer may not be generalizable to patients of different countries. Further studies are needed to clarify whether sociodemographic, epidemiological and cultural scenarios may seriously affect the prognostic ability of newly developed predictive tools.

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Single Arm Phase II Trial of Elective Nodal Dose Reduction for Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

Publication date: Available online 28 December 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Patrick D. Maguire, Charles R. Neal, Stuart M. Hardy, Andrew M. Schreiber
PurposeTo evaluate a novel chemoradiotherapy (CRT) regimen for patients with squamous cell carcinoma of the head and neck (SCCHN) incorporating a lower intensity modulated radiation therapy (IMRT) dose to electively treated neck lymph nodes than is currently standard.Methods and MaterialsEligible patients had locally advanced SCCHN of the oral cavity, oropharynx, larynx, or hypopharynx. The seven week CRT course consisted of weekly cisplatin at 35 mg/m2 concurrent with sequential boost IMRT: 36 Gy to high and low risk planning target volumes (PTV) followed by a sequential boost to high risk PTV to 70 Gy. The primary endpoint was elective nodal failure (ENF). Secondary endpoints were survival, toxicity, feeding tube duration, and QOL evaluated by FACT-HN and QOL-RTI surveys.ResultsBetween 2011 and 2014, 54 patients were enrolled, 31 (57%) of whom had HPV+ disease. Thirty-five (65%) patients had stage IVa disease. Median follow-up for survivors was 36 months (range 12 - 66 months). No patient developed ENF. Actuarial three-year survival for the entire cohort was 91 % (95% confidence interval [CI] 0.79-0.96); HPV- 85% (95% CI 0.61-0.95), and HPV+ 96% (95% CI 0.77-0.99). Common grade three toxicities were dysphagia 79%, mucositis/stomatitis 41%, nausea 20%, xerostomia 13%, vomiting 11%, and neutropenia 10%. Median feeding tube duration was 142 days. Patient FACT-HN scores were higher at three, six, and 12 months vs. end of treatment (p<0.0001). Total FACT-HN scores returned to pre-treatment baseline by six months. Overall QOL-RTI scores were lower from pre-treatment to end of treatment through 12 months (p=0.0001).ConclusionThis CRT regimen for patients with advanced SCCHN demonstrated the potential feasibility of reducing the elective dose to the neck, a topic that requires additional study in future clinical trials.

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Real-time whole brain radiotherapy: A single institution experience

Publication date: Available online 28 December 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Anh H. Le, Strahinja Stojadinovic, Robert Timmerman, Hak Choy, Romona L. Duncan, Steve B. Jiang, Arnold Pompos
PurposeTo demonstrate the feasibility of a real-time whole brain radiation therapy (WBRT). The study takes advantage of contemporary radiotherapy capabilities and seeks to optimize clinical workflow for WBRT.MethodsWe developed a method incorporating the linac's on-board imaging system for patient simulation, utilized cone beam computed tomography (CBCT) data for treatment planning and delivered first fraction of prescribed therapy, all during patient's initial appointment. Simulation was performed in the linac vault. An acquired CBCT data set was used for scripted treatment planning protocol providing inversely planned, automated treatment plan generation. The osseous boundaries of the brain were auto-contoured to create a target volume. Two parallel-opposed beams utilizing field-in-field IMRT covered this target to the user-defined inferior level (C1 or C2). The method was commissioned utilizing an anthropomorphic head phantom and verified using 100 clinically treated patients.ResultsWhole brain target heterogeneity was within 95% to 107% of the prescription dose and target coverage compared favorably to standard manually created 3D plans. For the commissioning CBCT datasets, the secondary monitor unit (MU) verification and independent 3D dose distribution comparison for computed and delivered doses were within 2% agreement relative to the scripted auto plans. On average, time needed to complete the entire process was (35.1±10.3) minutes from CBCT start to last beam delivered.ConclusionsThe real-time WBRT workflow using integrated on-site imaging, planning, quality assurance, and delivery was tested and deemed clinically feasible. The design necessitates a synchronized team consisting of physician, physicist, dosimetrist and therapists. This work serves as a proof of concept of real time planning and delivery for other treatment sites.

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Does seed migration increase the risk of second malignancies in prostate cancer patients treated with I-125 loose seeds brachytherapy?

Publication date: Available online 28 December 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Éric Vigneault, Kevin Martell, Daniel Taussky, Siraj Husain, Guila Delouya, Khaly Mbodji, Julie Piotte, Sindy Magnan, Philippe Després, Marie-Claude Lavallée, Sylviane Aubin, Luc Beaulieu, William Foster, André-Guy Martin
PurposeTo evaluate the risk of second malignancies after migration of seeds (MS) in prostate cancer patients treated with I-125 loose seeds brachytherapy.Materials and MethodsData from 2802 prostate cancer patients treated with I-125 loose seeds brachytherapy in three Canadian centres were reviewed. After seeds implant, all patients underwent post implant pelvic radiography and CT scan for post implant dosimetry. These images were used to assess if seed migration occurred. The incidence of second malignancies was determined through the review of patient's chart. The 7- and 10-year cumulative incidences of second malignancies and their 95% confidence intervals were calculated. Fine and Gray competing risk regression analysis was used to assess the factors associated with the development of a second malignancies.ResultsMean age and median follow-up was 63.5 years and 74 (range 12-246) months. MS occurred in 263 of 2802 patients (9.4%). Second malignancies occurred in 87 (3.1%) patients for the entire cohort and was not different between patients who experienced MS (9, 3.4%) or not (78, 3.1%) (p=0.755). The 7-year cumulative incidence rates of second malignancies were 2.95% (1.20%-6.00%) (with MS) vs. 2.82% (2.10%-3.70%) (without MS) (p=0.756). The corresponding values at 10-years were 6.16% (2.20%-12.3%) vs.4.51% (3.20%-5.50%) (p=0.570). MS did not appear to be a significant predictor factor for second malignancies development (adjusted HR 1.27 [95%CI, 0.63-2.55]; p=0.510). In both model, only advanced age was significantly associated with second malignancies development.ConclusionThese results did not show an increased risk of second malignancies associated with MS after I-125 loose seeds brachytherapy for prostate cancer patients. Longer follow-up and more events are required to better correlate MS and second malignancies.

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Standing on a sliding board affects generation of anticipatory and compensatory postural adjustments

Publication date: Available online 28 December 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Bing Chen, Yun-Ju Lee, Alexander S. Aruin
Postural control is compromised in the presence of body instability. We studied anticipatory and compensatory postural adjustments people use to maintain balance while standing on an unstable surface and performing voluntary arm movements. Nine healthy participants stood on a sliding board (that was either locked and as such motionless or unlocked and as such free to move in the anterior-posterior direction) and performed fast bilateral arms flexion. Arm acceleration, bilateral electromyographic activity (EMG) of the trunk and lower extremity muscles and center of pressure (COP) displacements were recorded and analyzed within the intervals typical for the anticipatory (APAs) and compensatory (CPAs) postural adjustments. Peaks of acceleration of the arm movements were not different between the locked and unlocked conditions. Larger EMG integrals were seen in the muscles of the lower extremity in both APAs and CPAs when standing on the unlocked sliding board. No significant difference was observed in the trunk muscles. Larger maximum COP displacement was seen when participants stood on the locked board. The results demonstrated that when standing on a free to move sliding board and performing bilateral arm flexion, the central nervous system (CNS) does not slow down the arm movements; instead it modifies activation of the lower extremity muscles. The observed differences in APAs and CPAs between the locked and unlocked conditions suggest that the CNS employs similar strategy while controlling the focal part of the task and adjusts the activity of muscles that are close to the source of instability to control postural task.

http://ift.tt/2BPkseT

Tyrosyl-tRNA synthetase: a potential kyotorphin synthetase in mammals

Publication date: Available online 28 December 2017
Source:Peptides
Author(s): Tamotsu Tsukahara, Shuhei Yamagishi, Hiroyuki Neyama, Hiroshi Ueda
Kyotorphin (KTP; L-tyrosyl-L-arginine), an opioid-like analgesic discovered in the bovine brain, is potentially a neuromodulator because of its localization in synaptosomes, the existence of a specific KTP receptor, and the presence of its biosynthetic enzyme in the brain. KTP is formed in the brain from its constituent amino acids, L-tyrosine and L-arginine, by an enzyme termed KTP synthetase. However, the latter has never been identified. We aimed to test the hypothesis that tyrosyl-tRNA synthetase (TyrRS) is also KTP synthetase. We found that recombinant hTyrRS synthesizes KTP from tyrosine, arginine, and ATP, with Km = 1400 μM and 200 μM for arginine and tyrosine, respectively. TyrRS knockdown of PC12 cells with a small interfering RNA (siRNA) in the presence of 1.6 mM tyrosine, arginine, proline, or tryptophan significantly reduced the level of KTP, but not those of tyrosine-tyrosine, tyrosine-proline, or tyrosine-tryptophan. siRNA treatment did not affect cell survival or proliferation. In mice, TyrRS levels were found to be greater in the midbrain and medulla oblongata than in other brain regions. When arginine was administered 2 h prior to brain dissection, the KTP levels in these regions plus olfactory bulb significantly increased, although basal brain KTP levels remained relatively even. Our conclusion is further supported by a positive correlation across brain regions between TyrRS expression and arginine-accelerated KTP production.

http://ift.tt/2BRGDBb

Guanylin and uroguanylin mRNA expression is increased following Roux-en-Y gastric bypass, but guanylins do not play a significant role in body weight regulation and glycemic control

Publication date: Available online 28 December 2017
Source:Peptides
Author(s): María L. Fernandez-Cachon, Søren L. Pedersen, Kristoffer T. Rigbolt, Chen Zhang, Katrine Fabricius, Henrik H. Hansen, Lisbeth Elster, Lisbeth N. Fink, Matthias Schäfer, Nicolai A. Rhee, Ebbe Langholz, Erik Wandall, Steffen U. Friis, Peter Vilmann, Viggo B. Kristiansen, Christina Schmidt, Kay Schreiter, Kristin Breitschopf, Thomas Hübschle, Tina Jorsal, Tina Vilsbøll, Thorsten Schmidt, Stefan Theis, Filip K. Knop, Philip Just Larsen, Jacob Jelsing
AimTo determine whether intestinal expression of guanylate cyclase activator 2A (GUCA2A) and guanylate cyclase activator 2B (GUCA2B) genes is regulated in obese humans following Roux-en-Y gastric bypass (RYGB), and to evaluate the corresponding guanylin (GN) and uroguanylin (UGN) peptides for potentially contributing to the beneficial metabolic effects of RYGB.MethodsEnteroendocrine cells were harvested peri- and post-RYGB, and GUCA2A/GUCA2B mRNA expression was compared. GN, UGN and their prohormones (proGN, proUGN) were administered subcutaneously in normal-weight mice to evaluate effects on food intake and glucose regulation. The effect of pro-UGN or UGN overexpression, using adeno-associated virus (AAV) vectors, was assessed in diet-induced obese (DIO) mice. Intracerebroventricular administration of GN and UGN was performed in rats for assessment of putative centrally mediated effects on food intake. GN and UGN, as well as their prohormones, were evaluated for effects on glucose-stimulated insulin secretion (GSIS) in rat pancreatic islets and perfused rat pancreas.ResultsGUCA2A and GUCA2B mRNA expression was significantly upregulated in enteroendocrine cells after RYGB. Peripheral administration of guanylins or prohormones did not influence food intake, oral glucose tolerance, and GSIS. Central administration of GN and UGN did not affect food intake in rats. Chronic AVV-mediated overexpression of UGN and proUGN had no effect on body weight or glucose homeostasis in DIO mice.ConclusionGN and UGN, as well as their prohormones, do not seem to play a significant role in body weight regulation and glycemic control, suggesting that guanylin-family peptides do not show promise as targets for the treatment of obesity or diabetes.

http://ift.tt/2BRGr4V

The octapetide NAP alleviates intestinal and extra-intestinal anti-inflammatory sequelae of acute experimental colitis

Publication date: Available online 27 December 2017
Source:Peptides
Author(s): Markus M. Heimesaat, Eliezer Giladi, Anja A. Kühl, Stefan Bereswill, Illana Gozes
The octapeptide NAP has been shown to exert neuroprotective properties and reduce neuro-inflammatory responses. The aim of the present study was to investigate if NAP provides anti-inflammatory effects in acute murine colitis. To address this, C57BL/6 j mice were challenged with 3.5% dextran sulfate sodium from day 0 until day 6 to induce colitis, either treated intraperitoneally with NAP or placebo (NaCl 0.9%) from day 1 until day 6 post-induction (p.i.) and subjected to in depth macroscopic, microscopic and immunological evaluations. Whereas NAP application did not alleviate macroscopic (i.e. clinical) sequelae of colitis, lower numbers of apoptotic, but higher counts of proliferating/regenerating colonic epithelial cells could be observed in NAP as compared to placebo treated mice at day 7 p.i. Furthermore, lower numbers of adaptive immune cells such as T lymphocytes and regulatory T cells were abundant in the colonic mucosa and lamina propria upon NAP versus placebo treatment that were accompanied by less colonic secretion of pro-inflammatory mediators including IFN-γ and nitric oxide at day 7 p.i. In mesenteric lymph nodes, pro-inflammatory IFN-γ, TNF and IL-6 concentrations were increased in placebo, but not NAP treated mice at day 7 p.i., whereas interestingly, elevated anti-inflammatory IL-10 levels could be observed in NAP treated mice only. The assessed anti-inflammatory properties of NAP were not restricted to the intestinal tract, given that in extra-intestinal compartments such as the kidneys, IFN-γ levels increased in placebo, but not NAP treated mice upon colitis induction. NAP induced effects were accompanied by distinct changes in intestinal microbiota composition, given that colonic luminal loads of bifidobacteria, regarded as anti-inflammatory, "health-promoting" commensal species, were two orders of magnitude higher in NAP as compared to placebo treated mice and even naive controls. In conclusion, NAP alleviates intestinal and extra-intestinal pro-inflammatory sequelae of acute experimental colitis and may provide novel treatment options of intestinal inflammatory diseases in humans.

http://ift.tt/2lccar0

Intraepithelial CD8 (+) Lymphocytes as a Predictive Diagnostic Biomarker for the Remission of Oral Lichen Planus

Publication date: Available online 28 December 2017
Source:Human Pathology
Author(s): Ai Enomoto, Eiichi Sato, Takashi Yasuda, Tatsuya Isomura, Toshitaka Nagao, Daichi Chikazu
Oral lichen planus (OLP) is an autoimmune inflammatory disease of the oral mucosa whose etiology remains unknown. Moreover, the possibility of OLP being a premalignant change is under debate. Various types of immune cells infiltrate the OLP lesion and affect its clinicopathological features. However, the diversity of infiltrating immune cells has not been fully clarified in relation to OLP diagnosis. In this study, we quantitatively examined CD8 (+) lymphocyte infiltration by immunohistochemistry, which is the principal effector of cytotoxic immune reaction in 123 cases of OLP specimens. Our examination revealed that high-grade intraepithelial CD8 (+) lymphocyte infiltration was associated with a high remission rate. Evaluation of the infiltration of T-bet (+) and FoxP3 (+) lymphocytes, which corresponded to the Th1 and Treg CD4 (+) subsets, respectively, showed that intraepithelial CD8 (+) lymphocytes were associated with the remission rate in the subgroup with a higher T-bet/FoxP3 subset balance that is inducible for cytotoxic immunity. We also investigated the cut-off value of CD8 (+) lymphocyte infiltration for histopathological diagnosis. By microscopic counting, '16 cells/high power field', which was also confirmed in the validation cohort, was established as the cut-off value for intraepithelial CD8 (+) lymphocyte infiltration for predicting the remission of OLP. Remitting OLP might be different from refractory OLP in terms of etiology and clinical behavior. Thus, intraepithelial CD8 (+) lymphocytes may serve not only as a predictive biomarker for remission but also as an area for further biomedical research regarding the etiology and premalignant potential of OLP.

http://ift.tt/2C58xO6

Startles, Stiffness and SLC6A5: Do You Know the Condition?

Publication date: Available online 28 December 2017
Source:Pediatric Neurology
Author(s): Arushi Gahlot Saini, Takeshi Taketani, Jitendra Kumar Sahu, Pratibha Singhi

http://ift.tt/2ldyNLK

Surgical management and outcomes of colorectal cancer liver metastases

Publication date: Available online 28 December 2017
Source:Cancer Epidemiology
Author(s): Eva Morris, Tom Treasure

http://ift.tt/2CdZF89

Questioning the Dietary Acculturation Paradox: A Mixed-Methods Study of the Relationship between Food and Ethnic Identity in a Group of Mexican-American Women

Publication date: Available online 28 December 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): A. Susana Ramírez, Tanya Golash-Boza, Jennifer B. Unger, Lourdes Baezconde-Garbanati
BackgroundEpidemiological studies have described an "acculturation paradox." Increased acculturation to the United States is associated with increased consumption of dietary fat and decreased consumption of fruits/vegetables.ObjectiveTo expand understanding of the dietary acculturation paradox, this study examined how bicultural Mexican-American women construct ethnic identity and how these identities and identity-making processes relate to perceptions of health and nutrition.DesignWe utilized embedded mixed methods (in-depth interviews; survey).Participants/settingWe analyzed a purposive sample of English-speaking Mexican-American women aged 18 to 29 years (n=24) in rural California to assess ethnic identity and diet beliefs.ResultsParticipants described food as central to expressing cultural identity, usually in terms of family interactions. Mexican food traditions were characterized as unhealthy; many preferred American foods, which were seen as healthier. Specifically, Mexican-American women perceived Mexican patterns of food preparation and consumption as unhealthy. In addition, traditional Mexican foods described as unhealthy were once considered special-occasion foods. Among the participants who expressed a desire to eat healthfully, to do so meant to reject Mexican ways of eating.ConclusionsThis study raises questions about the nature of the "dietary acculturation paradox." While food—the eating of Mexican foods—is central to the maintenance of ethnic identity throughout acculturation, negative perceptions about the healthfulness of Mexican foods introduce tension into Mexican-American women's self-identification. This study suggests a subtle contradiction that may help to explain the dietary acculturation paradox: While previous research has suggested that as Mexicans acculturate to the United States they adopt unhealthy diets, this study finds evidence that they do so at least in part due to perceptions that American diets are healthier than Mexican diets. Implications for interventions to improve Latinos' diets include an emphasis on the family and use of Spanish linguistic cues. Finally, messages that simply advocate for "traditional" diets should be reconsidered because that message is discordant with perceptions of the healthfulness of such foods.

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Nutrition and Cancer Research: Resources for the Nutrition and Dietetics Practitioner

Publication date: Available online 28 December 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Nancy J. Emenaker, Ashley J. Vargas

http://ift.tt/2lcdytS

Drosophila Perpetuates Nutritional Mutualism by Promoting the Fitness of Its Intestinal Symbiont Lactobacillus plantarum

Publication date: Available online 28 December 2017
Source:Cell Metabolism
Author(s): Gilles Storelli, Maura Strigini, Théodore Grenier, Loan Bozonnet, Martin Schwarzer, Catherine Daniel, Renata Matos, François Leulier
Facultative animal-bacteria symbioses, which are critical determinants of animal fitness, are largely assumed to be mutualistic. However, whether commensal bacteria benefit from the association has not been rigorously assessed. Using a simple and tractable gnotobiotic model— Drosophila mono-associated with one of its dominant commensals, Lactobacillus plantarum—we reveal that in addition to benefiting animal growth, this facultative symbiosis has a positive impact on commensal bacteria fitness. We find that bacteria encounter a strong cost during gut transit, yet larvae-derived maintenance factors override this cost and increase bacterial population fitness, thus perpetuating symbiosis. In addition, we demonstrate that the maintenance of the association is required for achieving maximum animal growth benefits upon chronic undernutrition. Taken together, our study establishes a prototypical case of facultative nutritional mutualism, whereby a farming mechanism perpetuates animal-bacteria symbiosis, which bolsters fitness gains for both partners upon poor nutritional conditions.

Graphical abstract

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Storelli et al. describe a mechanism whereby Drosophila larvae maintain their association with beneficial symbiotic bacteria. Symbiotic bacteria hasten the growth of undernourished larvae, while larvae secrete maintenance factors allowing bacteria to persist despite the shortage of their nutritional resources. Thus, Drosophila/bacteria symbiosis is a case of facultative nutritional mutualism.

http://ift.tt/2lnliZ1

Inner tooth morphology of Homo erectus from Zhoukoudian. New evidence from an old collection housed at Uppsala University, Sweden

Publication date: March 2018
Source:Journal of Human Evolution, Volume 116
Author(s): Clément Zanolli, Lei Pan, Jean Dumoncel, Ottmar Kullmer, Martin Kundrát, Wu Liu, Roberto Macchiarelli, Lucia Mancini, Friedemann Schrenk, Claudio Tuniz
Locality 1, in the Lower Cave of the Zhoukoudian cave complex, China, is one of the most important Middle Pleistocene paleoanthropological and archaeological sites worldwide, with the remains of c. 45 Homo erectus individuals, 98 mammalian taxa, and thousands of lithic tools recovered. Most of the material collected before World War II was lost. However, besides two postcranial elements rediscovered in China in 1951, four human permanent teeth from the 'Dragon Bone Hill,' collected by O. Zdansky between 1921 and 1923, were at the time brought to the Paleontological Institute of Uppsala University, Sweden, where they are still stored. This small sample consists of an upper canine (PMU 25719), an upper third molar (PMU M3550), a lower third premolar crown (PMU M3549), and a lower fourth premolar (PMU M3887). Some researchers have noted the existence of morpho-dimensional differences between the Zhoukoudian and the H. erectus dental assemblage from Sangiran, Java. However, compared to its chrono-geographical distribution, the Early to Middle Pleistocene dental material currently forming the Chinese-Indonesian H. erectus hypodigm is quantitatively meager and still poorly characterized for the extent of its endostructural variation. We used micro-focus X-ray tomography techniques of virtual imaging coupled with geometric morphometrics for comparatively investigating the endostructural conformation (tissue proportions, enamel thickness distribution, enamel-dentine junction morphology, pulp cavity shape) of the four specimens stored in Uppsala, all previously reported for their outer features. The results suggest the existence of time-related differences between continental and insular Southeast Asian dental assemblages, the Middle Pleistocene Chinese teeth apparently retaining an inner signature closer to the likely primitive condition represented by the Early Pleistocene remains from Java, while the Indonesian stock evolved toward tooth structural simplification.

http://ift.tt/2Dsbnc1

The effect of 2-hydroxypropyl-β-cyclodextrin on the intestinal permeation through mucus

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Jef Stappaerts, Philippe Berben, Irem Cevik, Patrick Augustijns
In addition to its important role in preventing the interaction of toxic agents with the intestinal lining, the intestinal mucus layer can impede the permeation of drugs. The purpose of this study was to evaluate whether the presence of HP-β-CD in the intraluminal environment could influence the permeation of drugs through a layer of mucus. To this end, a new artificial membrane insert system incorporating a fixed mucus layer was developed to monitor the permeation of methylparaben (log P=1.96) and heptylparaben (log P=4.83). While the transport of methylparaben remained unaffected by the mucus layer, the transport of heptylparaben was significantly impeded by the mucus layer. In presence of relatively low concentrations of HP-β-CD, however, this negative effect of mucus on the permeation of heptylparaben disappeared. Importantly, the impact of the mucus layer was found to depend on the composition of the solvent system used. The colloidal structures present in simulated intestinal media were able to neutralize the impeding effect of mucus on heptylparaben permeation observed when using simple phosphate buffers. These findings advocate the use of biorelevant media when studying the impact of the mucus layer on drug permeation.

Graphical abstract

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Editorial Board

Publication date: January 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 1

http://ift.tt/2pOsp2p

Publication date: January 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 1

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Editors' Selections From This Issue: Volume 99 / Number 1 / January 2018

Publication date: January 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 1

http://ift.tt/2pSvMFA

Masthead

Publication date: January 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 1

http://ift.tt/2E6DG11

Rasch Analyses of the Wheelchair Use Confidence Scale for Power Wheelchair Users

Publication date: January 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 1
Author(s): Brodie M. Sakakibara, William C. Miller, Paula W. Rushton, Jan Miller Polgar
ObjectivesTo examine the dimensionality of the Wheelchair Use Confidence Scale for power wheelchair users (WheelCon-P), to identify items that do not fit the Rasch rating scale model as well as redundant items for elimination, and to determine the SEMs and reliability estimates for the entire range of measurements.DesignSecondary analysis of cross-sectional data.SettingCommunity.ParticipantsVolunteer participants (N=189) using wheelchairs (mean age of the sample, 56.7±13.0y; mean years of wheelchair use experience, 20.4±16.4).InterventionsNot applicable.Main Outcome Measures59-Item WheelCon-P.ResultsPrincipal component analyses confirmed the presence of 2 self-efficacy dimensions: mobility and social situation. Eleven mobility items and 5 social situation items fit the Rasch rating scale model. Three items misfit the model using all 16 items (ie, WheelCon-P short form). In each of the mobility, social situation, and WheelCon-P short form range of measurements, the 2 lowest and 2 highest measures had internal consistency reliability estimates below .70; all other measures had reliability estimates above .70.ConclusionsThe WheelCon-P is composed of 2 self-efficacy dimensions related to mobility and social situations. The scores from the WheelCon-P short form and the 11-item mobility and 5-item social situation dimensions using a 0 to 10 response scale have good reliability.

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Correction

Publication date: January 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 1

http://ift.tt/2Eal007

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