Speciation, mobilization, and bioaccessibility of arsenic in geogenic soil profile from Hong Kong.

Abstract: The behaviour of arsenic (As) from geogenic soil exposed to aerobic conditions is critical to predict the impact of As on the environment, which processes remain unresolved. The current study examined the depth profile of As in geologically derived subsoil cores from Hong Kong and investigated the mobilization, plant availability, and bioaccessibility of As in As-contaminated soil at different depths (0-45.8 m). Results indicated significant heterogeneity, with high levels of As in three layers of soil reaching up to 505 mg/kg at a depth of 5 m, 404 mg/kg at a depth of 15 m, and 1510 mg/kg at a depth of 27-32 m. Arsenic in porewater samples was <11.5 μg/L in the study site. X-ray absorption spectroscopy (XAS) indicated that main As species in soil was arsenate (As(V)), as adsorbed fraction to Fe oxides (41-69% on goethite and 0-8% on ferrihydrite) or the mineral form scorodite (30-57%). Sequential extraction procedure demonstrated that 0.5 ± 0.4% of As was exchangeable. Aerobic incubation experiments exhibited that a very small amount (0.14-0.48 mg/kg) of As was desorbed from the soil because of the stable As(V) complex structure on abundant Fe oxides (mainly goethite), where indigenous microbes partly (59 ± 18%) contributed to the release of As comparing with the sterilized control. Furthermore, no As toxicity in the soil was observed with the growth of ryegrass. The bioaccessibility of As was <27% in the surface soil using simplified bioaccessibility extraction test. Our systematic evaluation indicated that As in the geogenic soil profile from Hong Kong is relatively stable exposing to aerobic environment. Nevertheless, children and workers should avoid incidental contact with excavated soil, because high concentration of As was present in the digestive solution (<0.1-268 μg/L).

Cui|Jin-Li|JL|
Zhao|Yan-Ping|YP|
Li|Jiang-Shan|JS|
Beiyuan|Jing-Zi|JZ|
Tsang|Daniel C W|DCW|
Poon|Chi-Sun|CS|
Chan|Ting-Shan|TS|
Wang|Wen-Xiong|WX|
Li|Xiang-Dong|XD|

Mobility
Bioaccessibility
Fe oxide
Aerobic incubation
Arsenic biogeochemistry


Characterisation of capillary ionic liquid columns for gas chromatography-mass spectrometry analysis of fatty acid methyl esters.

Abstract: Due to their distinct chemical properties, the application of ionic liquid (IL) compounds as gas chromatography (GC) stationary phases offer unique GC separation especially in the analysis of geometric and positional fatty acid methyl ester (FAME) isomers. Elution behaviour of FAME on several commercialised IL capillary columns including phosphonium based SLB-IL59, SLB-IL60, SLB-IL61 and SLB-IL76 and imidazolium based SLB-IL82, SLB-IL100, and SLB-IL111 as well as a general purpose column SLB-5ms, were evaluated in gas chromatography-mass spectrometry (GC-MS) analysis. The phases were further characterised by using a linear solvation energy relationship (LSER) approach according to the equivalent chain length (ECL) index of FAME. Among all tested IL columns, elution temperatures of saturated FAME increased as their McReynolds' polarity value decreased, except for IL60. ECL values increased markedly as the stationary phase polarity increased, particularly for the polyunsaturated FAME. The LSER study indicated a lowest l/e value at 0.864 for IL111, displaying phase selectivity towards unsaturated FAME, with higher peak capacity within a carbon number isomer group. s and e descriptors calculated from LSER were validated by excellent correlation with dipole moments and lowest unoccupied molecular orbital (LUMO) energies, with R(2) values of 0.99 and 0.92 respectively, calculated using GAUSSIAN.

Zeng|Annie Xu|AX|
Chin|Sung-Tong|ST|
Nolvachai|Yada|Y|
Kulsing|Chadin|C|
Sidisky|Leonard M|LM|
Marriott|Philip J|PJ|

Equivalent chain length
Abraham descriptors
Fatty acid separation
High resolution gas chromatography
Ionic liquid phases


Epigenetics in the treatment of systemic lupus erythematosus: potential clinical application.

Abstract: The current treatments of systemic lupus erythematosus (SLE) have been based on the use of immunosuppressive drugs which are linked to serious side effects. The more effective therapeutic approaches with minimal or no side effects for SLE patients are hard to develop, mainly due to the complexity of the disease. The discovery of pharmacoepigenetics provides a new way to solve this problem. Epigenetic modifications can influence drug efficacy by altering gene expression via changing chromatin structure. Although still in early development, epigenetic studies in SLE are expected to reveal novel therapeutic targets and disease biomarkers in autoimmunity. For example, miRNAs, which have been identified to govern many genes including drug targets, are altered in disease development and after drug administration. This review aims to present an overview of current epigenetic mechanisms involved in the pathogenesis of SLE, and discuss their potential roles in clinical and pharmacological applications.

Guo|Yu|Y|
Sawalha|Amr H|AH|
Lu|Qianjin|Q|

Systemic lupus erythematosus (SLE)
Pharmacoepigenetics
Biomarkers
DNA methylation
HDAC inhibitors
microRNA


Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States.

Abstract: Pre-existing HIV drug resistance can jeopardize first-line antiretroviral therapy (ART) success. Changes in the prevalence of drug resistance-associated mutations (DRMs) were analyzed from HIV-infected, ART-naive, U.S. individuals seeking ART treatment from 2000 to 2009. HIV DRM data from 3,829 ART-naive subjects were analyzed by year of sample collection using International Antiviral Society-United States (IAS-USA) and World Health Organization (WHO) "surveillance" DRM definitions; minor IAS-USA-defined DRMs were excluded. IAS-USA DRM prevalence between 2000 and 2009 was 14%, beginning with 8% in 2000 and 13% in 2009. The greatest incidence was observed in 2007 (17%). Overall, IAS-USA-defined non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs were 9.5%; nucleoside reverse transcriptase inhibitor (NRTI): 4%, and major protease inhibitor (PI): 3%. The most frequently detected IAS-USA-defined DRMs by class were NNRTI: K103N/S (4%), NRTI: M41L (1.5%), and PI: L90M (1%). Overall, WHO-defined DRM prevalence was 13% (5% in 2000; 13% in 2009). By class, NNRTI prevalence was 6%, NRTI: 6%, and PI: 3.2%. The most frequent WHO-defined DRMs were NRTI: codon T215 (3.0%), NNRTI: K103N/S (4%), and PI: L90 (1%). WHO-defined NNRTI DRMs declined significantly (p = .0412) from 2007 to 2009. The overall prevalence of HIV-1 containing major IAS-USA or WHO-defined DRMs to ≥2 or ≥3 classes was 2% and <1%, respectively. The prevalence of HIV-1 with WHO-defined dual- or triple-class resistance significantly declined (p = .0461) from 2008 (4%) to 2009 (<1%). In this U.S. cohort, the prevalence of HIV-1 DRMs increased from 2000 onward, peaked between 2005 and 2007, and then declined between 2008 and 2009; the detection of WHO-defined dual- or triple-class DRM similarly decreased from 2008 to 2009.

Ross|Lisa L|LL|
Shortino|Denise|D|
Shaefer|Mark S|MS|

HIV-1
NNRTI mutation transmission
antiretroviral drug resistance
antiretroviral-naive
surveillance mutations
transmitted drug resistance


Dual-potential electrochemiluminescence of single luminophore for detection of biomarker based on black phosphorus quantum dots as co-reactant.

Abstract: Simultaneous cathodic and anodic electrochemiluminescence (ECL) emissions of needle-like nanostructures of Ru(bpy)32+ (RuNDs) as the only luminophore are reported based on different co-reactants. Cathodic ECL was attained from RuNDs/K2S2O8 system, while anodic ECL was achieved from RuNDs/black phosphorus quantum dots (BPQDs) system. Ferrocene attached to the hairpin DNA could quench the cathodic and anodic ECL simultaneously. Subsequently, the ECL signals recovered in the presence of tumor marker mucin 1 (MUC1), which made it possible to quantitatively detect MUC1. The variation of ECL signal was related linearly to the concentrations of MUC1 in the range 20 pg mL-1 to 10 ng mL-1, and the detection limits were calculated to 2.5 pg mL-1 (anodic system, 3σ) and 6.2 pg mL-1 (cathodic system, 3σ), respectively. The recoveries were 97.0%, 105%, and 95.2% obtained from three human serum samples, and the relative standard deviation (RSD) is 5.3%. As a proof of concept, this work realized simultaneous ECL emission of  a single luminophore, which initiates a new thought in biomarker ECL detection beyond the traditional ones. Simultaneous cathodic and anodic ECL emissions of RuNDs were reported based on different co-reactants. Ferrocene could quench the ECL emission in the cathode and the anode simultaneously. Thus, an aptasensor was constructed based on the variation of ECL intensity. As a proof of concept, this work realized simultaneous ECL emission of a single luminophore, which initiates a new thought in biomarker ECL detection beyond the traditional ones by avoiding the false positive signals.

Yin|Hao|H| Shi|YaHao|Y| Liu|Hui|H| Dong|YongPing|Y| Chu|XiangFeng|X|

Electrochemiluminescence
Biomarker
Black phosphorus
Quantum dots
Tumor marker mucin 1
Aptasensor


Antipulverization Electrode Based on Low-Carbon Triple-Shelled Superstructures for Lithium-Ion Batteries.

Abstract: The realization of antipulverization electrode structures, especially using low-carbon-content anode materials, is crucial for developing high-energy and long-life lithium-ion batteries (LIBs); however, this technology remains challenging. This study shows that SnO2 triple-shelled hollow superstructures (TSHSs) with a low carbon content (4.83%) constructed by layer-by-layer assembly of various nanostructure units can withstand a huge volume expansion of ≈231.8% and deliver a high reversible capacity of 1099 mAh g-1 even after 1450 cycles. These values represent the best comprehensive performance in SnO2 -based anodes to date. Mechanics simulations and in situ transmission electron microscopy suggest that the TSHSs enable a self-synergistic structure-preservation behavior upon lithiation/delithiation, protecting the superstructures from collapse and guaranteeing the electrode structural integrity during long-term cycling. Specifically, the outer shells during lithiation processes are fully lithiated, preventing the overlithiation and the collapse of the inner shells; in turn, in delithiation processes, the underlithiated inner shells work as robust cores to support the huge volume contraction of the outer shells; meanwhile, the middle shells with abundant pores offer sufficient space to accommodate the volume change from the outer shell during both lithiation and delithiation. This study opens a new avenue in the development of high-performance LIBs for practical energy applications.

antipulverization
lithium-ion batteries
SnO2
carbon
triple-shelled structure


Birth of an order: Comprehensive molecular phylogenetic study excludes Herpomyces (Fungi, Laboulbeniomycetes) from Laboulbeniales.

Abstract: The class Laboulbeniomycetes comprises biotrophic parasites associated with arthropods and fungi. Two orders are currently recognized, Pyxidiophorales and Laboulbeniales. Herpomyces is an isolated genus of Laboulbeniales, with species that exclusively parasitize cockroaches (Blattodea). Here, we evaluate 39 taxa of Laboulbeniomycetes with a three-locus phylogeny (nrSSU, ITS, nrLSU) and propose a new order in this class. Herpomycetales accommodates a single genus, Herpomyces, with currently 26 species, one of which is described here based on morphological and molecular data. Herpomyces shelfordellae is found on Shelfordella lateralis cockroaches from Hungary, Poland, and the USA. We also build on the six-locus dataset from the Ascomycota Tree of Life paper (Schoch and colleagues, 2009) to confirm that Laboulbeniomycetes and Sordariomycetes are sister classes, and we apply laboulbeniomyceta as a rankless taxon for the now well-resolved node that describes the most recent common ancestor of both classes.

Haelewaters|Danny|D|
Pfliegler|Walter P|WP|
Gorczak|Michał|M|
Pfister|Donald H|DH|

Laboulbeniomycetes
Cockroaches
Phylogeny
Divergence times
Ectoparasitic fungi


Poly aspartic acid peptide-linked PLGA based nanoscale particles: potential for bone-targeting drug delivery applications.

Abstract: Delivering drugs specifically to bone tissue is very challenging due to the architecture and structure of bone tissue. Poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) hold great promise for the delivery of therapeutics to bone tissue. The goal of the present research was to formulate a PLGA-based NP drug delivery system for bone tissue exclusively. Since poly-aspartic acids (poly-Asp) peptide sequence has been shown to bind to hydroxyapatite (HA), and has been suggested as a molecular tool for bone-targeting applications, we fabricated PLGA-based NPs linked with poly-Asp peptide sequence. Nanoparticles made of methoxy - poly(ethylene glycol) (PEG)-PLGA and maleimide-PEG-PLGA were prepared using a water-in-oil-in-water double emulsion and solvent evaporation method. Fluorescein isothiocyanate (FITC)-tagged poly-Asp peptide was conjugated to the surface of the nanoparticles via the alkylation reaction between the sulfhydryl groups at the N-terminal of the peptide and the CC double bond of maleimide at one end of the polymer chain to form thioether bonds. The conjugation of FITC-tagged poly-Asp peptide to PLGA NPs was confirmed by NMR analysis and fluorescent microscopy. The developed nanoparticle system is highly aqueous dispersible with an average particle size of ∼80 nm. In vitro binding analyses demonstrated that FITC-poly-Asp NPs were able to bind to HA gel as well as to mineralized matrices produced by human mesenchymal stem cells and mouse bone marrow stromal cells. Using a confocal microscopy technique, an ex vivo binding study of mouse major organ ground sections revealed that the FITC-poly-Asp NPs were able to bind specifically to the bone tissue. In addition, proliferation studies indicated that our FITC-poly-Asp NPs did not induce cytotoxicity to human osteoblast-like MG63 cell lines. Altogether, these promising results indicated that this nanoscale targeting system was able to bind to bone tissue specifically and might have a great potential for bone disease therapy in clinical applications.

Jiang|Tao|T|
Yu|Xiaohua|X|
Carbone|Erica J|EJ|
Nelson|Clarke|C|
Kan|Ho Man|HM|
Lo|Kevin W-H|KW|

D000077182:Polylactic Acid-Polyglycolic Acid Copolymer

Nanoparticles
Peptides
Bone diseases
Targeted drug delivery


Assembling the Community-Scale Discoverable Human Proteome.

Abstract: The increasing throughput and sharing of proteomics mass spectrometry data have now yielded over one-third of a million public mass spectrometry runs. However, these discoveries are not continuously aggregated in an open and error-controlled manner, which limits their utility. To facilitate the reusability of these data, we built the MassIVE Knowledge Base (MassIVE-KB), a community-wide, continuously updating knowledge base that aggregates proteomics mass spectrometry discoveries into an open reusable format with full provenance information for community scrutiny. Reusing >31 TB of public human data stored in a mass spectrometry interactive virtual environment (MassIVE), the MassIVE-KB contains >2.1 million precursors from 19,610 proteins (48% larger than before; 97% of the total) and doubles proteome coverage to 6 million amino acids (54% of the proteome) with strict library-scale false discovery controls, thereby providing evidence for 430 proteins for which sufficient protein-level evidence was previously missing. Furthermore, MassIVE-KB can inform experimental design, helps identify and quantify new data, and provides tools for community construction of specialized spectral libraries.

Wang|Mingxun|M|
Wang|Jian|J|
Carver|Jeremy|J|
Pullman|Benjamin S|BS|
Cha|Seong Won|SW|
Bandeira|Nuno|N|

proteomics
knowledge base
spectral libraries
algorithms
big data
repositories
tandem mass spectrometry


Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation.

Abstract: The threshold of toxicological concern (TTC) approach is a resource-effective de minimis method for the safety assessment of chemicals, based on distributional analysis of the results of a large number of toxicological studies. It is being increasingly used to screen and prioritize substances with low exposure for which there is little or no toxicological information. The first step in the approach is the identification of substances that may be DNA-reactive mutagens, to which the lowest TTC value is applied. This TTC value was based on the analysis of the cancer potency database and involved a number of assumptions that no longer reflect the state-of-the-science and some of which were not as transparent as they could have been. Hence, review and updating of the database is proposed, using inclusion and exclusion criteria reflecting current knowledge. A strategy for the selection of appropriate substances for TTC determination, based on consideration of weight of evidence for genotoxicity and carcinogenicity is outlined. Identification of substances that are carcinogenic by a DNA-reactive mutagenic mode of action and those that clearly act by a non-genotoxic mode of action will enable the protectiveness to be determined of both the TTC for DNA-reactive mutagenicity and that applied by default to substances that may be carcinogenic but are unlikely to be DNA-reactive mutagens (i.e. for Cramer class I-III compounds). Critical to the application of the TTC approach to substances that are likely to be DNA-reactive mutagens is the reliability of the software tools used to identify such compounds. Current methods for this task are reviewed and recommendations made for their application.

Boobis|Alan|A|
Brown|Paul|P|
Cronin|Mark Timothy David|MTD|
Edwards|James|J|
Galli|Corrado Lodovico|CL|
Goodman|Jay|J|
Jacobs|Abigail|A|
Kirkland|David|D|
Luijten|Mirjam|M|
Marsaux|Cyril|C|
Martin|Matthew|M|
Yang|Chihae|C|
Hollnagel|Heli Miriam|HM|

Threshold of toxicological concern (TTC)


Ramachandran conformational energy maps for disaccharide linkages found in Burkholderia multivorans biofilm polysaccharides.

Abstract: Ramachandran conformational energy maps have been prepared for all of the glycosidic linkages found in the C1576 exopolysaccharide that constitutes the biofilms of the bacterial species Burkholderia multivorans, a member of the Burkholderia cepacian complex that was isolated from a cystic fibrosis patient. This polysaccharide is a rhamnomannan with a tetrasaccharide repeat unit containing two mannose residues and two rhamnose residues, -[3-α-d-Man-(1→2)-α-d-Man-(1→2)-α-d-Rha-(1→3)-α-d-Rha-(1→]n-, where approximately 50% of the rhamnoses are randomly methylated on their O3 hydroxyl groups, further increasing the overall hydrophobicity of the chains. Because of the methylation, the tetrasaccharide repeat unit actually contains six possible linkages. The conformational energy maps are fully adiabatic relaxed maps in which the energy for each (ϕ,ψ) grid point on the map represents the lowest possible energy for the molecule in that conformation, considering all the combinations of the other degrees of freedom, such as hydroxyl orientations. Molecular dynamics simulations were used to verify that these maps indeed describe the conformational dynamics of these linkages. All six linkages were found to be quite restricted in possible ϕ angles, but to exhibit several possible low-energy ψ angles, suggesting that these chains could be quite flexible.

Jou|Ining A|IA|
Caterino|Marco|M|
Schnupf|Udo|U|
Rizzo|Roberto|R|
Cescutti|Paola|P|
Brady|John W|JW|

Polysaccharide Ramachandran conformational energy maps


A sector-based dosimetric analysis of dose heterogeneity in high-dose-rate prostate brachytherapy.

Abstract:
PURPOSE
High-dose-rate (HDR) prostate brachytherapy delivers a heterogeneous dose distribution throughout the prostate gland. There is however limited information regarding the spatial distribution of this dose heterogeneity. To this end, we analyzed the magnitude and location of intraprostatic dose heterogeneity in HDR prostate brachytherapy.

METHODS AND MATERIALS
Five consecutive prostate cancer patients treated with HDR were analyzed. Based on CT-simulation images, each prostate was divided into three sections (apex, base, and mid-gland). These were further subdivided into eight symmetrical sections to give a total of 24 sections. Dose-volume histograms were analyzed from V100-V200% for these 24 sections comparing the means of individual regions, left vs right, apex vs base vs mid-gland, lateral vs medial, and anterior vs posterior. A separate analysis on dose as a function of individual region volume was also performed.

RESULTS
Analyses comparing the 24 regions showed a maximum 62% difference (range, 21.9-83.9%) at V130% and 19.9% (1.9-20.8%) at V200%. Seven regions were significantly decreased and one significantly elevated from V130-V180% when compared with the mean. The means for lateral sections were 1.57-fold higher than medial sections from V110-V200% (p < 0.0001). The dose at the base was significantly higher than the rest of the gland from V120-V200 (V150, 35.6 ± 16.2% vs 20.9 ± 13.1%, p < 0.0001).

CONCLUSIONS
There is significant intra-prostatic dose heterogeneity in prostate HDR brachytherapy. This is most notable in the increased dose to base and lateral portions of the gland. Further studies are needed to determine the impact of heterogeneity on clinical outcomes.

Mesko|Shane|S|
Park|Sang-June|SJ|
Kishan|Amar U|AU|
Demanes|D Jeffrey|DJ|
Kamrava|Mitchell|M|


Absence of a human ortholog of rodent Kupffer cell galactose-binding receptor encoded by the CLEC4f gene.

Abstract: The murine CLEC4f gene encodes the Kupffer cell receptor, a galactose-binding receptor containing a C-type carbohydrate-recognition domain. Orthologs have been identified in nearly 100 species. The receptors from rat and mouse have previously been characterized and data presented here show that functional CLEC4f protein is expressed in domestic cattle (Bos taurus). However, the human CLEC4f gene does not encode a functional receptor because a mutation in the splice acceptor site of the final exon prevents appropriate splicing and a missense mutation disrupts the sugar-binding site. Transcriptomic and PCR analysis of transcripts confirms the absence of a spliced transcript containing the final exon and only background levels of transcripts are detected in human tissues. These mutations are also present in the CLEC4f gene in Neanderthals. In contrast to humans, closely related species, including chimpanzees, do have CLEC4f genes that encode full-length receptors. Affinity chromatography and glycan array results demonstrate that the chimpanzee, bovine and murine proteins all bind to galactose, but they show preferences for different subsets of galactose-containing glycans. In non-human primates, the receptor is expressed in spleen rather than in liver. The results indicate that the CLEC4f protein probably has distinct functions in different species. Absence of the receptor precludes using it for targeting of glycoconjugates to cells in human liver. The fact that CLEC4f protein is expressed in spleen in non-human primates and the close evolutionary relationship of the CLEC4f protein to langerin (CD207) suggest that it may function in the immune system, possibly as a pathogen receptor.

Taylor|Maureen E|ME|
Snelling|Tom|T|
Smith|David F|DF|
Drickamer|Kurt|K|

transcriptomics
glycan array
evolution
glycan-binding receptor
lectin


Important Role of a Putative Lytic Transglycosylase Cj0843c in β-Lactam Resistance in Campylobacter jejuni.

Abstract: Beta-lactam antibiotics are an important class of antibiotics for treating bacterial infections. Despite prevalent β-lactam resistance in Campylobacter jejuni, the leading bacterial cause of human diarrhea in developed countries, molecular mechanism of β-lactam resistance in C. jejuni is still largely unknown. In this study, C. jejuni 81-176 was used for random transposon mutagenesis. Screening of a 2,800-mutant library identified 22 mutants with increased susceptibility to ampicillin. Of these mutants, two mutants contains mutations in Cj0843c (a putative lytic transglycosylase gene) and in its upstream gene Cj0844c, respectively. Complementation experiment demonstrated that the Cj0843 contributes to β-lactam resistance. The Cj0843c insertional mutation was subsequently introduced to diverse C. jejuni clinical strains for MIC test, showing that Cj0843c contributes to both intrinsic and acquired β-lactam resistance of C. jejuni. Consistent with this finding, inactivation of Cj0843c also dramatically reduced β-lactamase activity. Genomic examination and PCR analysis showed Cj0843c is widely distributed in C. jejuni. High purity recombinant Cj0843c was produced for generation of specific antiserum. The Cj0843 was localized in the periplasm, as demonstrated by immunoblotting using specific antibodies. Turbidimetric assay further demonstrated the capability of the purified Cj0843c to hydrolyze cell walls. Inactivation of Cj0843c also significantly reduced C. jejuni colonization in the intestine. Together, this study identifies a mechanism of β-lactam resistance in C. jejuni and provides insights into the role of cell wall metabolism in regulating β-lactamase activity.

lytic transglycosylase
random transposon mutagenesis
beta-lactamase
peptidoglycan


3D Printed Lithium-Metal Full Batteries Based on a High-Performance Three-Dimensional Anode Current Collector.

Abstract: A three-dimensional (3D) printing method has been developed for preparing a lithium anode base on 3D-structured copper mesh current collectors. Through in situ observations and computer simulations, the deposition behavior and mechanism of lithium ions in the 3D copper mesh current collector are clarified. Benefiting from the characteristics that the large pores can transport electrolyte and provide space for dendrite growth, and the small holes guide the deposition of dendrites, the 3D Cu mesh anode exhibits excellent deposition and stripping capability (50 mAh cm-2), high-rate capability (50 mA cm-2), and a long-term stable cycle (1000 h). A full lithium battery with a LiFePO4 cathode based on this anode exhibits a good cycle life. Moreover, a 3D fully printed lithium-sulfur battery with a 3D printed high-load sulfur cathode can easily charge mobile phones and light up 51 LED indicators, which indicates the great potential for the practicability of lithium-metal batteries with the characteristic of high energy densities. Most importantly, this unique and simple strategy is also able to solve the dendrite problem of other secondary metal batteries. Furthermore, this method has great potential in the continuous mass production of electrodes.

3D printing
deposition behavior
high-rate
lithium dendrites
lithium metal anode


The pedagogical effect of a health education application for deaf and hard of hearing students in elementary schools.

Abstract:
BACKGROUND
Deaf or hard-of-hearing children experience difficulties in learning health principles. But technology has significantly improved their ability to learn. The challenge in e-learning is to design attractive applications while having an educational aspect.

OBJECTIVE
The aims of this study were to determine the pedagogical effectiveness of a health education application for deaf and hard of hearing students in elementary schools, and to investigate the student's perceptions in different educational grades about the educational effectiveness of the text, graphics, video clips, and animation in the application.

METHODS
The study design was quasi experimental and was conducted in Mashhad in 2016. Study population were deaf or hard-of-hearing students in elementary schools. The intervention included health application training to deaf and hard-of-hearing students in Mashhad. A questionnaire was used for data gathering. The pedagogical effectiveness was determined by measuring the modified Adapted Pedagogical Index. This index was created based on the characteristics of the application and study population. Statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney tests with Bonferroni adjustment by SPSS 22.

RESULTS
Eighty-two students participated in the intervention. The value of modified Adapted Pedagogical Index was 0.669, indicating that the application was effective. The results of Kruskal-Wallis H and Mann-Whitney U test showed significant differences in different educational grades. (p<0.008).

CONCLUSION
Using information technology can improve the education of deaf and hard-of-hearing students. Modified Adapted Pedagogical Index can be used for evaluation of non-interactive applications for elementary school children who are deaf or hard of hearing.

Abbasi|Masoumeh|M| Eslami|Saeid|S| Mohammadi|Mahdi|M| Khajouei|Reza|R|

Health Education
Deafness
Student
Evaluation Studies
Hearing Disabled


Formation of a nona-nuclear copper(II) cluster with 3,5-di-methyl-pyrazolate starting from an NHC complex of copper(I) chloride.

Abstract: The complete nona-nuclear cluster in bis-[1,3-bis-(2,6-di-methyl-phen-yl)imid-azol-ium] di-μ-chlorido-tetra-chlorido-octa-kis-(μ-3,5-di-methyl-pyrazolato)hexa-μ3-hydroxido-nona-copper(II) chloro-form disolvate, [HIXy]2[Cu9(μ-pz*)8(μ3-OH)6(μ2-Cl)2Cl4]·2CHCl3 or (C19H21N2)2[Cu9(C5H7N2)8Cl6(OH)6]·2CHCl3, where pz* is the 3,5-di-methyl-pyrazolyl anion, C5H7N2 -, and HIXy is the 1,3-bis-(2,6-di-methyl-phen-yl)imidazolium cation, C19H21N2 +, is generated by a crystallographic centre of symmetry with a square-planar CuII ion bound to four μ3-OH ions lying on the inversion centre. Of the four remaining unique CuII atoms, three adopt CuN2O2Cl square-pyramidal coordination geometries with the chloride ion in the apical position and one has a distorted CuN2OCl tetra-hedral geometry. The dianionic nona-nuclear core can be described as a 24-membered [CuNN]8 ring that contains a Cu9O6Cl6 core. The cluster features three intra-molecular O-H⋯Cl hydrogen bonds. In the crystal, weak C-H⋯N and C-H⋯Cl inter-actions link the components. Polynuclear paramagnetic clusters of this type are of considerable inter-est due to their relevance to both the bioinorganic and single-mol-ecule magnets research fields.

cluster
N-heterocyclic carbene
copper
crystal structure


A genome wide association study identifies new genes potentially associated with eyelid sagging.

Abstract: Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10-10 ) and rs4746957 (P = 1.06 × 10-8 ), were significantly associated with eyelid sagging severity. The rs16927253-T and rs4746957-A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.

Laville|Vincent|V|0000-0003-4946-698X
Le Clerc|Sigrid|S|
Ezzedine|Khaled|K|
Jdid|Randa|R|0000-0002-0465-2474
Taing|Lieng|L|
Labib|Toufik|T|
Coulonges|Cédric|C|
Ulveling|Damien|D|
Galan|Pilar|P|
Guinot|Christiane|C|
Fezeu|Leopold|L|
Morizot|Frédérique|F|
Latreille|Julie|J|
Malvy|Denis|D|
Tschachler|Erwin|E|
Zagury|Jean-François|JF|

genome wide association study
skin ageing
genetic association
histone
epigenetics


Molecular analysis of circulating tumor DNA from breast cancer patients before and after surgery and following adjuvant chemotherapy.

Abstract: The primary aim of the present study is to provide a complex molecular profile of tumors using liquid biopsy and to monitor profile changes over time in association with surgery and administered adjuvant therapy. Our secondary aim was to compare the liquid biopsy profile with the tissue biopsy and assess concordance. A total of 27 samples of circulating tumor DNA (ctDNA) collected from 9 breast cancer patients at three different time points and their matched formalin-fixed and paraffin-embedded (FFPE) samples of primary tumor were analyzed with targeted next-generation sequencing. Somatic pathogenic variants were detected before surgery in samples from 5 patients (55.6%). The most frequently mutated genes were phosphatase and tensin homolog (4/9, 44.4%) and tumor protein 53 (4/9, 44.4%). Serial sampling of ctDNA enabled the detection of more variants compared with single-time tissue primary tumor biopsy. There were 17 ctDNA variants across all samples, but only 6 FFPE variants across all patients. In addition, the concordance between ctDNA and FFPE DNA was determined in only 1 patient, and this was connected with higher variant allele frequency. The findings of the present study suggest that liquid biopsy and tissue biopsy may be used as complementary analyses to adequately capture all tumor variants.

Zelinova|Katarina|K| Jagelkova|Marianna|M| Laucekova|Zuzana|Z| Bobrovska|Martina|M| Dankova|Zuzana|Z| Grendar|Marian|M| Dokus|Karol|K|

circulating tumor DNA
breast cancer
liquid biopsy
next-generation sequencing
serial monitoring


Fattening of Polish Holstein-Friesian × Limousin Bulls under Two Production Systems and Its Effect on the Fatty Acid Profiles of Different Fat Depots.

Abstract: This study was designed to compare the fatty acid (FA) profiles of four types of fat depots from crossbred bulls (Polish Holstein-Friesian × Limousin, PHF × LM) fattened semi-intensively (SI) and intensively (I). Intramuscular fat was most abundant in total polyunsaturated fatty acids (PUFAs), n-3 and n-6 PUFAs, and functional fatty acids C 18:2, C 18:3, C 20:4 and C 20:5 in comparison with the remaining fat types. Furthermore, note that external fat was more abundant in conjugated linoleic acid (CLA) than other fat types. Grass silage fed to cattle during fattening had a beneficial influence on the FA profile of beef, and an increase in the amount of concentrate in the ration did not decrease beef quality.

production system
fatty acids
fat depot
beef


Knowledge, attitudes and behaviours of patients regarding interdental deplaquing devices: A mixed-methods study.

Abstract:
OBJECTIVES
This mixed-methods study assessed patients' oral health literacy, motivation level and barriers regarding interdental plaque control.

METHODS
Participants (n = 49) from a study comparing the use of Glide® Pro-Health Floss Original (F) or GUM® Curved Soft-Picks® Advance (SP) completed daily diaries and questionnaires regarding motivation, tiredness, confidence and satisfaction for their deplaquing method. The Mantel-Haenszel chi-square test was utilized. Data were also collected from 19 participants who attended focus group discussions regarding their oral health habits, knowledge, motivators and barriers with interdental plaque control. Discussions were digitally recorded, transcribed and imported into ATLAS.ti 7.5.15 to identify themes.

RESULTS
There were no statistically significant differences between the two groups in relation to age, sex or ethnicity. F users reported statistically significant higher agreement about ability to remove food/debris (P = 0.01), cleaning thoroughly (P = 0.02) and clean feeling of the mouth (P = 0.01). SP users reported higher ease/efficiency of use (P = 0.01), convenience (P = 0.003), easy to hold (P = 0.0001) and easy use away from home (P = 0.008). Daily diaries revealed higher motivation and compliance/ease of use (SP). During the focus groups, some reported that they did not feel clean unless they deplaqued interdentally; however, most reported that they lacked motivation due to constraints on time, no desire due to lack of immediate or tangible rewards, and lack of knowledge on proper use of interdental devices or the benefits of using them.

CONCLUSION
This study showed that the lack of compliance may be due to poor literacy and lack of motivation in patients due to gaps in patient education.

D003742:Dental Devices, Home Care
D003773:Dental Plaque
D005891:Gingivitis
D006801:Humans
D009909:Oral Health
D010349:Patient Compliance

health literacy
motivation
dental devices
home care
patient compliance
periodontal diseases


"Purple Drank" (Codeine and Promethazine Cough Syrup): A Systematic Review of a Social Phenomenon with Medical Implications.

Abstract: In the early 1990s, several studies reported the misuse of codeine and promethazine hydrochloride cough syrup. Since then, the combination of this pharmaceutical, together with sprite or alcohol, known on the streets as "purple drank" or "lean", has become a popular drug among rap singers who promote its tranquilizing and euphoric effects through their music and videos. This review examines the "purple drank" phenomenon, taking into consideration its clinical and social implications. The study was conducted using PubMed, Scopus, and Web of Science as search engines, applying several inclusion and exclusion criteria and the string "Purple AND drank", resulting in 138 records. Seven papers that met our criteria were found. The risk of bias assessment, when applicable, was also considered, resulting in a low level of risk. Epidemiological data highlighted a heterogeneous diffusion of the misuse of this mixture, which is not exclusively linked to a specific type of user (African-American teenagers, athletes, and rappers), as previously reported in American newspapers and in the social media. New digital tools should be taken into consideration for further social and medical evaluations of this phenomenon.

Miuli|A|A|
Stigliano|G|G|0000-0001-9078-3851
Lalli|A|A|
Coladonato|M|M|
D'Angelo|L|L|
Esposito|F|F|
Cappello|C|C|
Pettorruso|M|M|
Martinotti|G|G|
Schifano|F|F|
Di Giannantonio|M|M|

Purple Drank
codeine abuse
opioids
promethazine abuse
social subgroups


Why tocilizumab could be an effective treatment for severe COVID-19?

Abstract: A severe pneumonia-associated respiratory syndrome caused by a new coronavirus was identified in December 2019 (COVID-19), spread rapidly and has become a world-wide public health challenge. About 25% of COVID-19 patients experienced severe complications including acute respiratory distress syndrome (ARDS), and even progressed into an intensive care unit (ICU) admission and died. The exploration for the mortality causes and advancing novel therapeutic development of severe COVID-19 is crucial at the moment. The biopsy samples analysis at autopsy suggested that increased alveolar exudate caused by aberrant host immune response and inflammatory cytokine storm probably impedes alveolar gas exchange and contributes to the high mortality of severe COVID-19 patients. Our research has identified that pathogenic T cells and inflammatory monocytes incite inflammatory storm with large amount of interleukin 6, therefore monoclonal antibody that targets the IL-6 pathways may potentially curb inflammatory storm. Moreover, Tocilizumab treatment that blocking IL-6 receptors showed inspiring clinical results including temperature returned to normal quickly and respiratory function improved. Therefore, we suggest that Tocilizumab is an effective treatment in severe patients of COVID-19 to calm the inflammatory storm and reduce mortality.

Acute respiratory distress syndrome (ARDS)


Impact of interpersonal relations on learning and development of professional identity: A study of residents' perceptions.

Abstract:
OBJECTIVES
Informal learning includes all occurrences during one's life when learning is not deliberate. Prior research on informal learning in healthcare contexts examined learning happening outside of the formal curriculum, yet still in the workplace. This study explores residents' perceptions about extracurricular factors outside of the workplace that contribute to their learning and development of professional identity, whether interpersonal relations are recognised as such factors, and positive and negative impacts of interpersonal relations.

METHODS
In this qualitative study, all 21 residents in our Emergency Medicine programme were asked, in a web-based survey with open-ended questions, to identify extracurricular sources outside of the workplace perceived as contributing to their learning and professional identity development, and list positive and negative impacts of interpersonal relations outside of work on learning and identity development. Themes were extracted through content analysis of the narrative responses. Two reviewers coded all data.

RESULTS
Thirteen (62%) residents identified 37 factors grouped under five themes: learning activity, role modelling, support, non-clinical academic roles, and social interactions. Interpersonal relations were perceived as having positive and negative impacts, including creating support, positive role modelling and mentoring, increasing concrete learning, as well as lapses in teaching skills, deficits in professional role training, and loss of personal time.

CONCLUSIONS
Several extracurricular factors outside of the workplace contribute to resident learning and identity development, including interpersonal relations, which have positive and negative impacts. The most often noted negative impact of interpersonal relations outside of work between residents and faculty related to perceived lapses in teaching skills.

interpersonal relations
learning
emergency medicine
education
qualitative research


Multiple Pituitary Apoplexy-Cavernous Sinus Invasion as Major Risk Factor for Recurrent Hemorrhage.

Abstract:
OBJECTIVE
Pituitary apoplexy is a rare but potentially life-threatening disorder that occurs in up to 10% of adenomas. Whereas risk factors for the initial hemorrhagic event are well described, there is minor knowledge on clinical symptomatic recurrent pituitary apoplexies.

METHODS
At the Medical University of Vienna, 76 patients were surgically treated for clinical symptomatic pituitary apoplexy between 1990 and 2017. Four patients (5.3%) suffered multiple pituitary apoplexies after initial surgery. In this retrospective study, neuroradiologic images, clinical data, and intraoperative findings were reviewed for potential risk factors of multiple apoplexies in pituitary adenomas.

RESULTS
Patients with multiple apoplexies had significantly higher Knosp grading on preoperative imaging (median grade 4), and more frequently observed cavernous sinus invasion intraoperatively (P = 0.01). Consequently, all cases with multiple pituitary apoplexies remained with residual adenoma postoperatively. In cases of residual tumor within the cavernous sinus, recurrent apoplexy occurred in 23.5% of patients. A tumor recurrence/residual was resected significantly earlier in patients with single apoplexy (median 2.2 years) than in patients with multiple apoplexies (median 5.4 years; P = 0.05). Multiple pituitary apoplexies caused significantly greater rates of ophthalmoplegia (75% vs. 14.1%; P = 0.01) and long-term hormone-replacement therapy was necessary in all cases.

CONCLUSIONS
Cavernous sinus invasion and subtotal resection are high risk factors for multiple apoplexies in pituitary adenomas. Early treatment is recommended for residual tumor in the cavernous sinus to minimize the risk of recurrent apoplexy with subsequent worse clinical outcome.

Hosmann|Arthur|A|
Micko|Alexander|A|
Frischer|Josa M|JM|
Roetzer|Thomas|T|
Vila|Greisa|G|
Wolfsberger|Stefan|S|
Knosp|Engelbert|E|

Pituitary apoplexy
Pituitary adenoma
Cavernous sinus
Transsphenoidal


Probiotic Streptococcus thermophilus FP4 and Bifidobacterium breve BR03 Supplementation Attenuates Performance and Range-of-Motion Decrements Following Muscle Damaging Exercise.

Abstract: Probiotics have immunomodulatory effects. However, little is known about the potential benefit of probiotics on the inflammation subsequent to strenuous exercise. In a double-blind, randomized, placebo controlled, crossover design separated by a 21-day washout, 15 healthy resistance-trained men ingested an encapsulated probiotic Streptococcus (S.) thermophilus FP4 and Bifidobacterium (B.) breve BR03 at 5 bn live cells (AFU) concentration each, or a placebo, daily for 3 weeks prior to muscle-damaging exercise (ClinicalTrials.gov NCT02520583). Isometric strength, muscle soreness, range of motion and girth, and blood interleukin-6 (IL-6) and creatine kinase (CK) concentrations were measured from pre- to 72 h post-exercise. Statistical analysis was via mixed models and magnitude-based inference to the standardized difference. Probiotic supplementation resulted in an overall decrease in circulating IL-6, which was sustained to 48 h post-exercise. In addition, probiotic supplementation likely enhanced isometric average peak torque production at 24 to 72 h into the recovery period following exercise (probiotic-placebo point effect ±90% CI: 24 h, 11% ± 7%; 48 h, 12% ± 18%; 72 h, 8% ± 8%). Probiotics also likely moderately increased resting arm angle at 24 h (2.4% ± 2.0%) and 48 h (1.9% ± 1.9%) following exercise, but effects on soreness and flexed arm angle and CK were unclear. These data suggest that dietary supplementation with probiotic strains S. thermophilus FP4 and B. breve BR03 attenuates performance decrements and muscle tension in the days following muscle-damaging exercise.

Jäger|Ralf|R|
Purpura|Martin|M|
Stone|Jason D|JD|
Turner|Stephanie M|SM|
Anzalone|Anthony J|AJ|
Eimerbrink|Micah J|MJ|
Pane|Marco|M|
Amoruso|Angela|A|
Rowlands|David S|DS|
Oliver|Jonathan M|JM|

inflammation
cytokines
eccentric exercise
isokinetic


Medicinal Plant Polyphenols Attenuate Oxidative Stress and Improve Inflammatory and Vasoactive Markers in Cerebral Endothelial Cells during Hyperglycemic Condition.

Abstract: Blood-brain barrier endothelial cells are the main targets of diabetes-related hyperglycemia that alters endothelial functions and brain homeostasis. Hyperglycemia-mediated oxidative stress may play a causal role. This study evaluated the protective effects of characterized polyphenol-rich medicinal plant extracts on redox, inflammatory and vasoactive markers on murine bEnd3 cerebral endothelial cells exposed to high glucose concentration. The results show that hyperglycemic condition promoted oxidative stress through increased reactive oxygen species (ROS) levels, deregulated antioxidant superoxide dismutase (SOD) activity, and altered expression of genes encoding Cu/ZnSOD, MnSOD, catalase, glutathione peroxidase (GPx), heme oxygenase-1 (HO-1), NADPH oxidase 4 (Nox4), and nuclear factor erythroid 2-related factor 2 (Nrf2) redox factors. Cell preconditioning with inhibitors of signaling pathways highlights a causal role of nuclear factor kappa B (NFκB), while a protective action of AMP-activated protein kinase (AMPK) on redox changes. The hyperglycemic condition induced a pro-inflammatory response by elevating NFκB gene expression and interleukin-6 (IL-6) secretion, and deregulated the production of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), and nitric oxide (NO) vasoactive markers. Importantly, polyphenolic extracts from Antirhea borbonica, Ayapana triplinervis, Dodonaea viscosa, and Terminalia bentzoe French medicinal plants, counteracted high glucose deleterious effects by exhibiting antioxidant and anti-inflammatory properties. In an innovative way, quercetin, caffeic, chlorogenic and gallic acids identified as predominant plant polyphenols, and six related circulating metabolites were found to exert similar benefits. Collectively, these findings demonstrate polyphenol protective action on cerebral endothelial cells during hyperglycemic condition.

oxidative stress
cerebral endothelial cells
hyperglycemia
antioxidant plant polyphenols
inflammation


Intestinal overexpression of IL-18 promotes eosinophils-mediated allergic disorders.

Abstract: Baseline eosinophils reside in the gastrointestinal tract; however, in several allergic disorders, excessive eosinophils accumulate in the blood as well in the tissues. Recently, we showed in vitro that interleukin (IL)-18 matures and transforms IL-5-generated eosinophils into the pathogenic eosinophils that are detected in human allergic diseases. To examine the role of local induction of IL-18 in promoting eosinophil-associated intestinal disorders, we generated enterocyte IL-18-overexpressing mice using the rat intestinal fatty acid-binding promoter (Fabpi) and analysed tissue IL-18 overexpression and eosinophilia by performing real-time polymerase chain reaction, Enzyme-Linked Immunosorbent Assay and anti-major basic protein immunostaining. Herein we show that Fabpi-IL-18 mice display highly induced IL-18 mRNA and protein in the jejunum. IL-18 overexpression in enterocytes promotes marked increases of eosinophils in the blood and jejunum. Our analysis shows IL-18 overexpression in the jejunum induces a specific population of CD101+  CD274+ tissue eosinophils. Additionally, we observed comparable tissue eosinophilia in IL-13-deficient-Fabpi-IL-18 mice, and reduced numbers of tissue eosinophils in eotaxin-deficient-Fabpi-IL-18 and IL-5-deficient-Fabpi-IL-18 mice compared with Fabpi-IL-18 transgenic mice. Notably, jejunum eosinophilia in IL-5-deficient-Fabpi-IL-18 mice is significantly induced compared with wild-type mice, which indicates the direct role of induced IL-18 in the tissue accumulation of eosinophils and mast cells. Furthermore, we also found that overexpression of IL-18 in the intestine promotes eosinophil-associated peanut-induced allergic responses in mice. Taken together, we provide direct in vivo evidence that induced expression of IL-18 in the enterocytes promotes eotaxin-1, IL-5 and IL-13 independent intestinal eosinophilia, which signifies the clinical relevance of induced IL-18 in eosinophil-associated gastrointestinal disorders (EGIDs) to food allergens.

Verma|Alok K|AK|
Kandikattu|Hemanth Kumar|HK|
Manohar|Murli|M|
Shukla|Anshi|A|
Upparahalli Venkateshaiah|Sathisha|S|
Zhu|Xiang|X|
Mishra|Anil|A|0000-0003-4266-4684

IL-18 eosinophils Fabpi EGID eotaxin peanut


Educating Latinas about cervical cancer and HPV: a pilot randomized study.

Abstract:
INTRODUCTION
The purpose of this study was to assess effects of three different educational intervention arms on knowledge of and intention to receive Pap testing and HPV co-testing.

METHODS
Three active educational intervention arms were developed: a fotonovela, a radionovela, and a digital story. A pilot randomized controlled trial of 160 Latinas was conducted to assess the effectiveness of the intervention arms in increasing knowledge of cervical cancer and HPV and intention to be screened for cervical cancer compared to an attention control group (flu vaccination).

RESULTS
Women in all three treatment arms significantly increased knowledge about cervical cancer compared to control arm (p = 0.02). Knowledge about cervical cancer screening also increased in the active arms compared to control (p = 0.0003). Knowledge of HPV risk also increased relative to the control (p = 0.0001). There were no significant differences between the intervention arms in increased knowledge of cervical cancer or cervical cancer screening (p = 0.57 and 0.16, respectively).

DISCUSSION
This study supported the use of small media interventions in narrative education form as effective in increasing knowledge and intention to be screened for cervical cancer. The three culturally relevant interventions, built on qualitative data, were all successful in increasing knowledge.

Thompson|Beti|B|
Barrington|Wendy E|WE|
Briant|Katherine J|KJ|
Kupay|Erin|E|
Carosso|Elizabeth|E|
Gonzalez|Nora E|NE|
Gonzalez|Virginia J|VJ|

D000328:Adult
D055088:Early Detection of Cancer
D005260:Female
D006630:Hispanic or Latino
D006801:Humans
D008875:Middle Aged
D030361:Papillomavirus Infections
D010865:Pilot Projects
D002583:Uterine Cervical Neoplasms
D014611:Vaccination
D014626:Vaginal Smears
D055815:Young Adult

Education
Latinas
Cervical cancer
HPV
Fotonovela
Radionovela
Digital story


The Bladder Is a Novel Target of Developmental Polychlorinated Biphenyl Exposure Linked to Increased Inflammatory Cells in the Bladder of Young Mice.

Abstract: Bladder inflammation is associated with several lower urinary tract symptoms that greatly reduce quality of life, yet contributing factors are not completely understood. Environmental chemicals are plausible mediators of inflammatory reactions within the bladder. Here, we examine whether developmental exposure to polychlorinated biphenyls (PCBs) leads to changes in immune cells within the bladder of young mice. Female mice were exposed to an environmentally relevant mixture of PCBs through gestation and lactation, and bladders were collected from offspring at postnatal day (P) 28-31. We identify several dose- and sex-dependent PCB effects in the bladder. The lowest concentration of PCB (0.1 mg/kg/d) increased CD45+ hematolymphoid immune cells in both sexes. While PCBs had no effect on CD79b+ B cells or CD3+ T cells, PCBs (0.1 mg/kg/d) did increase F4/80+ macrophages particularly in female bladder. Collagen density was also examined to determine whether inflammatory events coincide with changes in the stromal extracellular matrix. PCBs (0.1 mg/kg/d) decreased collagen density in female bladder compared to control. PCBs also increased the number of cells undergoing cell division predominantly in male bladder. These results implicate perturbations to the immune system in relation to PCB effects on the bladder. Future study to define the underlying mechanisms could help understand how environmental factors can be risk factors for lower urinary tract symptoms.

Kennedy|Conner L|CL|
Spiegelhoff|Audrey|A|
Wang|Kathy|K|
Lavery|Thomas|T|
Nunez|Alexandra|A|
Manuel|Robbie|R|0000-0003-3761-8712
Hillers-Ziemer|Lauren|L|
Arendt|Lisa M|LM|
Stietz|Kimberly P Keil|KPK|

bladder
inflammation
lower urinary tract
POPs
developmental basis of adult disease


NK1 receptor antagonists as a new treatment for corneal neovascularization.

Abstract:
PURPOSE
To determine whether the inhibition of Substance P (SP) activity can reduce corneal neovascularization (CNV) by means of local administration of high-affinity, competitive, tachykinin 1 receptor (NK1R) antagonists Lanepitant and Befetupitant.

METHODS
We performed a safety and efficacy study by using (1) two different C57BL/6 mouse models of CNV: alkali burn and sutures; (2) different concentrations; and (3) different routes of administration: topical or subconjunctival. Clinical examination endpoints, SP levels, CNV index, and leukocyte infiltration were measured.

RESULTS
Substance P increased after injury in the corneal epithelium of both CNV models, and later in the suture model. Topical Lanepitant was nontoxic to the ocular surface and effective in reducing hemangiogenesis and lymphangiogenesis, corneal SP levels, and leukocyte infiltration, as soon as 4 days later in the alkali burn model. Topical Lanepitant, up to 7 days, was ineffective in the suture model. However, subconjunctival Lanepitant was effective in reducing lymphatic CNV, leukocyte infiltration, and SP levels in the suture model, after 10 days. Additionally, in the alkali burn model, subconjunctival Lanepitant significantly reduced blood CNV, corneal perforation rate, opacity, and leukocyte infiltration, and improved tear secretion. Finally, topical application of Befetupitant reduced CNV in the alkali burn model but was toxic owing to the vehicle (dimethyl sulfoxide [DMSO]); hence, Befetupitant was not tested in the suture model.

CONCLUSIONS
The NK1R antagonist Lanepitant is safe for the ocular surface and effective in reducing both corneal hemangiogenesis and lymphangiogenesis, and leukocyte infiltration. We suggest that inhibition of NK1R may represent an adjunctive tool in the treatment of CNV.

Bignami|Fabio|F| Giacomini|Chiara|C| Lorusso|Anna|A| Aramini|Andrea|A| Rama|Paolo|P| Ferrari|Giulio|G|

NK1 receptor
corneal neovascularization
Substance P
Lanepitant
neuropeptide


Exercise-induced peptide TAG-23 protects cardiomyocytes from reperfusion injury through regulating PKG-cCbl interaction.

Abstract: Recent studies have revealed that proper exercise can reduce the risk of chronic disease and is beneficial to the body. Peptides have been shown to play an important role in various pathological processes, including cardiovascular diseases. However, little is known about the role of exercise-induced peptides in cardiovascular disease. We aimed to explore the function and mechanism of TAG-23 peptide in reperfusion injury and oxidative stress. Treatment with TAG-23 peptide significantly improved cell viability, the mitochondrial membrane potential, and ROS levels and reduced LDH release, the apoptosis rate and caspase 3 activation in vitro. In vivo, TAG-23 ameliorated MI and heart failure induced by I/R or DOX treatment. Pull-down assays showed that TAG-23 can bind to PKG . The TAG-23-PKG complex inhibited PKG degradation through the UPS. We also identified cCbl as the E3 ligase of PKG and found that the interaction between these proteins was impaired by TAG-23 treatment. In addition, we provided evidence that TAG-23 mediated Lys48-linked polyubiquitination and subsequent proteasomal degradation. Our results reveal that a novel exercise-induced peptide, TAG-23, can inhibit PKG degradation by serving as a competitive binding peptide to attenuate the formation of the PKG-cCbl complex. Treatment with TAG-23 may be a new therapeutic approach for reperfusion injury.

Cheng|Zijie|Z| Zhang|Hao|H| Zhang|Li|L| Wang|Xuejun|X| Zhang|Qijun|Q| Feng|Mengwen|M| Hu|Deliang|D| Li|Hua|H| Qian|Lingmei|L|0000-0002-5603-3886

TAG-23
PKG
cCbl
Doxorubicin
Myocardial infarction


Sex determining region Y-box 12 (SOX12) promotes gastric cancer metastasis by upregulating MMP7 and IGF1.

Abstract: Metastasis is the major cause of poor survival and therapeutic failure in gastric cancer (GC). However, the molecular mechanisms underlying GC metastasis remain unclear. Here, we analyzed the expression patterns of sex determining region Y-box 12 (SOX12) in two independent cohorts of paired GC tissues and adjacent nontumor tissues and conducted in vitro and in vivo functional studies to determine the role of SOX12 in GC cells. High SOX12 expression in GC tissues was associated with increased frequency of recurrence and poorer patient survival. SOX12 overexpression increased GC cell migration, invasion and metastasis, whereas SOX12 downregulation decreased these behaviors. Reporter assays revealed that matrix metallopeptidase 7 (MMP7) and insulin-like growth factor 1 (IGF1) are transcriptional targets of SOX12 and indicated their requirement for SOX12-mediated GC metastasis. IGF1 induced SOX12 expression via the PI3K/AKT/CREB pathway, forming an IGF1/CREB/SOX12 feedback loop that contributed to GC metastasis. SOX12 expression correlated with MMP7 and IGF1 expression in GC tissues, and patients expressing SOX12 and either MMP7 or IGF1 had higher metastasis and recurrence rates and shorter survival than patients without that expression pattern. In conclusion, SOX12 is a novel prognostic biomarker and regulator of GC metastasis.

Du|Feng|F| Feng|Weibo|W| Chen|Sheng|S| Wu|Shengda|S| Cao|Tianyu|T| Yuan|Ting|T| Tian|Dean|D| Nie|Yongzhan|Y| Wu|Kaichun|K| Fan|Daiming|D| Xia|Limin|L|

D017362:Cyclic AMP Response Element-Binding Protein

D015972:Gene Expression Regulation, Neoplastic


Multiple Intracranial Tuberculomas with an Intra-medullary Spinal Cord Tuberculoma in a Pediatric Patient.

Abstract: Central nervous system (CNS) tuberculosis (TB), caused by Mycobacterium tuberculosis (MT), is a severe form of TB, which presents as meningitis, cerebritis, abscesses, spinal tuberculous arachnoiditis, and rarely tuberculomas. CNS TB is prevalent in the underdeveloped or developing world and is common in malnourished, alcoholics, children, young adults, immunocompromised, and cancer patients. Intracranial tuberculomas (ICT) can present with symptoms and signs of focal neurological deficits with or without systemic manifestations. ICT is the least common presentation of CNS TB. Medical management with anti-TB drugs and steroids is the mainstay of treatment, while surgical intervention is usually reserved for refractory cases. Here, we present the case of a 10-year-old Indian American girl with headaches, diplopia, fever, and neck pain diagnosed with ICT and intramedullary spinal cord tuberculoma.

Meegada|Sreenath|S| Gyamfi|Richmond|R| Muppidi|Vijayadershan|V| Dandu|Vasuki|V| Challa|Tejo|T|

intracranial tuberculoma
intra-medullary spinal cord tuberculoma
central nervous system tuberculosis
cerebral tuberculomas
disseminated tuberculosis


Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction.

Abstract: Adaptation of reproductive activity to environmental changes is essential for breeding success and offspring survival. In mammals, the reproductive system displays regular cycles of activation and inactivation which are synchronized with seasonal and/or daily rhythms in environmental factors, notably light intensity and duration. Thus, most species adapt their breeding activity along the year to ensure that birth and weaning of the offspring occur at a time when resources are optimal. Additionally, female reproductive activity is highest at the beginning of the active phase during the period of full oocyte maturation, in order to improve breeding success. In reproductive physiology, it is therefore fundamental to delineate how geophysical signals are integrated in the hypothalamo-pituitary-gonadal axis, notably by the neurons expressing gonadotropin releasing hormone (GnRH). Several neurochemicals have been reported to regulate GnRH neuronal activity, but recently two hypothalamic neuropeptides belonging to the superfamily of (Arg)(Phe)-amide peptides, RFRP-3 and kisspeptin, have emerged as critical for the integration of environmental cues within the reproductive axis. The goal of this review is to survey the current understanding of the role played by RFRP-3 in the temporal regulation of reproduction, and consider how its effect might combine with that of kisspeptin to improve the synchronization of reproduction to environmental challenges.

Angelopoulou|Eleni|E|
Quignon|Clarisse|C|
Kriegsfeld|Lance J|LJ|
Simonneaux|Valérie|V|

seasonal rhythm
daily rhythm
clock
kisspeptin, LH
melatonin
vasoactive intestinal peptide
vasopressin


Investigating the role of anodic potential in the biodegradation of carbamazepine in bioelectrochemical systems.

Abstract: Anode potential is a critical factor in the biodegradation of organics in bioelectrochemical systems (BESs), but research on these systems with complex recalcitrant co-substrates at set anode potentials is scarce. In this study, carbamazepine (CBZ) biodegradation in a BES was examined over a wide range of set anode potentials (-200 to +600 mV vs Ag/AgCl). Current generation and current densities were improved with the increase in positive anode potentials. However, at a negative potential (-200 mV), current generation was higher as compared to that for +000 and +200 mV. The highest CBZ degradation (84%) and TOC removal efficiency (70%) were achieved at +400 mV. At +600 mV, a decrease in CBZ degradation was observed, which can be attributed to a low number of active bacteria and a poor ability to adapt to high voltage. This study signified that BESs operated at optimum anode potentials could be used for enhancing the biodegradation of complex and recalcitrant contaminants in the environment.

Tahir|Khurram|K|
Miran|Waheed|W|
Nawaz|Mohsin|M|
Jang|Jiseon|J|
Shahzad|Asif|A|
Moztahida|Mokrema|M|
Kim|Bolam|B|
Azam|Mudassar|M|
Jeong|Sang Eun|SE|
Jeon|Che Ok|CO|
Lim|Seong-Rin|SR|
Lee|Dae Sung|DS|

Anode potential
Biodegradation
Carbamazepine
Bioelectrochemical system


Reduced Graphene Oxide/Silicon Nitride Composite for Cooperative Electromagnetic Absorption in Wide Temperature Spectrum with Excellent Thermal Stability.

Abstract: The fabrication of a sandwich-like composite that consists of reduced graphene oxide (RGO) and Si3N4 ceramic (RGO/Si3N4) was achieved through the combination of modified freeze-drying approach and chemical vapor infiltration process. Due to a hierarchical structure and a high ratio of ID/ IG (1.27), the RGO/Si3N4 exhibits an unprecedented high polarization relaxation loss (PRL), which accounts for 32% of the whole dielectric loss. The outstanding PRL endows the RGO/Si3N4 composites with unique temperature-independent dielectric properties and electromagnetic (EM) wave absorption performance. Even at a low absorbent content of only 0.16 wt %, the effective absorption bandwidth of RGO/Si3N4 composites can cover the whole X-band (8.2-12.4 GHz) at broad sample thicknesses ranging from 4.3 to 4.6 mm and temperatures ranging from 323 to 873 K. The mechanism for the enhancement of PRL and conductive loss was explicitly investigated. The outstanding absorption performance toward EM waves indicated that the resultant porous RGO/Si3N4 composite can be a promising candidate for the applications under elevated temperature.

reduced graphene oxide
polarization relaxation loss
temperature-independent
conductive loss
amorphous Si3N4


Structure-function relationship of the plant photosynthetic pigment-protein complex LHCII studied with molecular spectroscopy techniques.

Abstract: LHCII, the largest plant photosynthetic pigment-protein complex of photosystem II, is a most abundant membrane protein in living organisms and comprises approximately half of the pool of chlorophyll molecules in the biosphere. The principal role of this pigment-protein complex is to collect sunlight quanta and transfer electronic excitations toward the reaction centers, where the primary photosynthetic electric charge separation reactions take place. The LHCII protein, as a major protein component of the photosynthetic membranes, modulates also the structural and dynamic properties of the lipid phase of the membranes. According to the recent concepts, one of the physiological roles of LHCII is also a protection of the photosynthetic apparatus against oxidative damage caused by illumination with high intensity light. Detailed examination of all those physiological functions of LHCII, in relation to the complex structure, was possible owing to the application of several molecular spectroscopy techniques. Some examples of such studies are presented in this chapter. The examples of application of steady-state and time-resolved fluorescence spectroscopy, Fourier-transform infrared absorption spectroscopy, and resonance Raman scattering spectroscopy are presented and discussed.

LHCII
Photosynthetic membranes
Photoprotection
Photosynthetic antenna complexes
Protein IR spectroscopy


Progression of choroidal metastasis of ovarian serous cystoadenocarcinoma after intravitreal bevacizumab treatment.

Abstract: A 57-year-old woman presented to her ophthalmologist because of rapid deterioration in vision. Dilated funduscopic examination of the right eye showed an elevated, yellow-orange choroidal mass temporal to the fovea; a complete retinal detachment was present in the left eye. The patient was referred to an oncologist. Computerized tomography of the brain, thorax, abdomen, and pelvis were obtained. They revealed an 11-mm mass in the right parietal lobe, a 30-mm mass in the left temporal lobe, 23-mm mass in the right kidney, and multiple nodules in both lungs. Supported by published experience with intravitreal bevacizumab for choroidal metastasis, the patient was injected into the vitreous through the pars plana of the left eye. The tumor mass did not show signs of regression and the visual acuity was unchanged. The patient suffered from end-state complications tumor metastasis and expired one month after the invitreal injection.

Kuo|Irene C|IC|
Sambuelli|Ruben H|RH|
Bono|Javier|J|
Smith|Ricardo J|RJ|
Reviglio|Victor E|VE|

choroidal metastasis
ovarian serous cystoadenocarcinoma
intravitreal bevacizumab.


Methodological Aspects of Obtaining and Characterizing Composites Based on Biogenic Diatomaceous Silica and Epoxy Resins.

Abstract: Diatomaceous earth are sediments of unicellular algal skeletons with a well-defined hierarchical structure. Despite many tests conducted on systems using diatomaceous earth and epoxy resins, we can find many differences in the methods of acquisition and characteristics of the composite, which may considerably affect the results. In our study, we have conducted tests to verify the impact of the method of obtaining samples and the degassing of the composite on its mechanical properties and standard deviation. The samples were cast in glass moulds and silicone moulds and then subjected to testing for their mechanical and functional properties, imaging with the use of an optical microscope and a scanning electron microscope. The tests have shown that, for samples cast in glass moulds, there is no heterogeneity within the area of the tested sample, as in the case of samples cast in silicone moulds. Silicone moulds allow for quite effective self-degassing of the resin due to the large area-to-mass ratio, and the small remaining air vesicles have a limited effect on the mechanical properties of the samples. The filler used also played a significant role. For systems containing base and rinsed diatomite, it is clear that the degassing of mixtures increases the tensile strength. For treated diatomite, the elongation at break grew along with increasing filler concentration, while for base diatomite, the improvement was observed for flexural strength and impact strength. A non-modified epoxy resin shows a tensile strength at 19.91 MPa (silicone mould cast). At the same time, the degassed, glass mould-cast systems containing 12% of base and rinsed diatoms showed a tensile strength of 27.4 MPa and 44.7 MPa, respectively. We have also observed that the higher the filler concentration, the higher were the tensile strength values, which for the rinsed diatoms reached over 55.1 MPa and for the base diatoms were maximum of 43.8 MPa. The tests, therefore, constitute a set of guidelines and recommendations for testing with the use of fillers showing an extended inner structure.

epoxy resin
diatomaceous earth
degassing
glass mould
silicone mould
diatomite
bio-composite


The key factor limiting plant growth in cold and humid alpine areas also plays a dominant role in plant carbon isotope discrimination.

Abstract: Many environmental factors affect carbon isotope discrimination in plants, yet the predominant factor influencing this process is generally assumed to be the key growth-limiting factor. However, to our knowledge this hypothesis has not been confirmed. We therefore determined the carbon isotope composition (δ(13)C) of plants growing in two cold and humid mountain regions where temperature is considered to be the key growth-limiting factor. Mean annual temperature (MAT) showed a significant impact on variation in carbon isotope discrimination value (Δ) irrespective of study area or plant functional type with either partial correlation or regression analysis, but the correlation between Δ and soil water content (SWC) was usually not significant. In multiple stepwise regression analysis, MAT was either the first or the only variable selected into the prediction model of Δ against MAT and SWC, indicating that the effect of temperature on carbon isotope discrimination was predominant. The results therefore provide evidence that the key growth-limiting factor is also crucial for plant carbon isotope discrimination. Changes in leaf morphology, water viscosity and carboxylation efficiency with temperature may be responsible for the observed positive correlation between Δ and temperature.

Xu|Meng|M| Wang|Guoan|G| Li|Xiaoliang|X| Cai|Xiaobu|X| Li|Xiaolin|X| Christie|Peter|P| Zhang|Junling|J|

carbon isotope discrimination
key growth-limiting factor
temperature
alpine plants
water availability


The Multiple Facets of Iron Recycling.

Abstract: The production of around 2.5 million red blood cells (RBCs) per second in erythropoiesis is one of the most intense activities in the body. It continuously consumes large amounts of iron, approximately 80% of which is recycled from aged erythrocytes. Therefore, similar to the "making", the "breaking" of red blood cells is also very rapid and represents one of the key processes in mammalian physiology. Under steady-state conditions, this important task is accomplished by specialized macrophages, mostly liver Kupffer cells (KCs) and splenic red pulp macrophages (RPMs). It relies to a large extent on the engulfment of red blood cells via so-called erythrophagocytosis. Surprisingly, we still understand little about the mechanistic details of the removal and processing of red blood cells by these specialized macrophages. We have only started to uncover the signaling pathways that imprint their identity, control their functions and enable their plasticity. Recent findings also identify other myeloid cell types capable of red blood cell removal and establish reciprocal cross-talk between the intensity of erythrophagocytosis and other cellular activities. Here, we aimed to review the multiple and emerging facets of iron recycling to illustrate how this exciting field of study is currently expanding.

ferroportin
heme
hemoglobin
hemolysis
hepcidin
iron homeostasis


Prenatal bisphenol A exposure is associated with language development but not with ADHD-related behavior in toddlers from the Odense Child Cohort.

Abstract: Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities widely used in a variety of consumer products. The fetal brain is particularly sensitive to chemical exposures due to its rapid growth and complexity. Some studies have reported associationbetween maternal BPA exposure and behavior but few have assessed impact on cognitive development, and to our knowledge no studies have specifically assessed the impact on language development. We therefore assessed whether maternal urinary BPA concentration during pregnancy was associated with language development and attention-deficit and hyperactivity disorder (ADHD) symptoms in offspring aged 18-36 months in the prospective Odense Child Cohort. BPA was analyzed in 3rd trimester maternal fasting urine spot samples. Language development was addressed among 535 children using the Danish adaptation of the MacArthur-Bates Communicative Development Inventories at median age 21 months; ADHD traits were assessed by parents of 658 children using the Child Behavior Checklist for ages 1½-5 years at mean age 2.7 years. Associations were assessed using logistic regression models comparing children below the 15th percentile score for language and above the 85 percentiles score for ADHD with the other children while stratifying by sex and adjusting for maternal education, duration of breastfeeding and maternal urine phthalates. BPA was detected in 85.3% of the urine samples (median 1.2 ng/ml). Boys of mothers with BPA exposure in the highest tertile had an odds ratio of 3.70 (95% CI 1.34-10.21) of being in the lowest 15th percentile of vocabulary score compared to boys of mothers within the lowest tertile of BPA exposure after adjustment, whereas no association was found in girls. No clear dose-response relationship between maternal BPA and ADHD scores above the 85th percentile was found for either sex. Since early language development is a predictor of future reading skills and educational success, more epidemiological studies assessing BPA exposure and language skills are needed to confirm our findings.

Jensen|Tina Kold|TK|
Mustieles|Vicente|V|
Bleses|Dorthe|D|
Frederiksen|Hanne|H|
Trecca|Fabio|F|
Schoeters|Greet|G|
Andersen|Helle Raun|HR|
Grandjean|Philippe|P|
Kyhl|Henriette Boye|HB|
Juul|Anders|A|
Bilenberg|Niels|N|
Andersson|Anna-Maria|AM|

D001289:Attention Deficit Disorder with Hyperactivity

D011297:Prenatal Exposure Delayed Effects

Bisphenol A
Language
ADHD
Endocrine disruptors
Neurodevelopment


Update on the systemic management of radioactive iodine refractory differentiated thyroid cancer (Review).

Abstract: The incidence of differentiated thyroid cancer (DTC) has increased over the last few decades, though it remains to be a rare disease. The prognosis of DTC is excellent; its treatment includes surgery (near-/total thyroidectomy), which is usually followed by remnant thyroid bed ablation using radio-iodine, as well as a risk-stratified follow-ups, including hormone replacement. Treatment of patients who are non-responsive to radioactive iodine (RAI) remains a challenge. Targeted therapies for RAI refractory DTC act primarily through inhibition of cell proliferation, survival and angiogenesis. Tyrosine kinase inhibitors (TKI) have achieved prolonged responses and improved progression-free survival, thereby representing a shift in the treatment of advanced thyroid cancer. There will be number of targeted treatment options for this patient population in the near future. Evidence regarding which drug should be used first and whether there is crossover drug resistance between these drugs is still lacking. Clinicians should be able to choose precisely which patients should be treated with novel targeted therapies after taking into account the following facts: i) TKIs have still not demonstrated a survival benefit. ii) The adverse effects of long-lasting treatment with TKIs could worsen quality of life, which is mostly excellent in these patients before starting treatment with these agents.

iodine refractory
thyroid cancer
tyrosine kinase inhibitors


The Medicinal Chemistry of Nitrite as a Source of Nitric Oxide Signaling.

Abstract: Conventional understanding of nitric oxide (NO) signaling in biology is commonly based on the premise that it simply diffuses randomly from its site of production by NO synthases to its site of action or inactivation. This notion has been challenged on a systemic cardiovascular scale with the realization that NO has endocrine effects despite being unable to exist in blood for more than a few milliseconds. Investigation of this phenomenon has led to the understanding that many of the chemical pathways that consume NO may not render it inactive as once thought. Instead, many of NO's metabolic products are still capable of carrying out NO signaling, or participate in NO-independent signaling in their own right. Nitrite and nitrate are two such products of NO metabolism that were once thought to be inert at physiological concentrations but are now known to contribute to NO bioactivity. The activity of nitrate is dependent upon its reduction to nitrite by bacterial nitrate reductase activity in the mouth. Nitrite can be reduced to NO by several metal-containing proteins under hypoxic conditions, or by nonenzymatic reactions under acidic conditions. Reduction and oxidation products of nitrite metabolism may also result in the production of NO adducts with a wide array of biological functions. The following review provides a general overview of the basic pathways underlying the physiological activity of nitrate and nitrite, as well as insight into the therapeutic potential of these pathways.

Nitrite
nitric oxide
Nitrate
dinitrosyl iron complex
iron-nitrosyl
nitrosothiol


Barrier or stressor? The role of discrimination experiences in health service use.

Abstract:
BACKGROUND
Discrimination is a well-established stressor that is substantially associated with poor health and a known contributor to health inequalities. However, the role of discrimination in health service use is less explored. This study will take an intersectional approach to investigate differences in health service use and examine the role of discrimination experiences.

METHODS
Data on health service use were assessed in a diverse inner London sample of 1052 participants in the South East London Community Health (SELCoH) Study. Latent class analysis (LCA) was used to define classes of intersectional social status using multiple indicators of socioeconomic status (SES), ethnicity and migration status. Adjusted associations between intersectional social status and discrimination experiences with health service use indicators are presented.

RESULTS
Using latent class analysis allowed us to identify an intersectional social status characterized by multiple disadvantage that was associated with decreased secondary physical health service use and a class characterized by both privilege and disadvantage that was associated with increased health service use for mental disorder after controlling for age, gender and health status. Anticipated discrimination was also associated with increased service use for mental disorder in adjusted models. There was no evidence to suggest that discrimination experiences were acting as a barrier to health service use.

CONCLUSIONS
This study highlights the complex ways in which discrimination experiences may increase the need for health services whilst also highlighting differences in health service use at the intersection of ethnicity, migration status and SES. Findings from this study illustrate the importance of measuring multiple levels of discrimination and taking an intersectional approach for health service use research.

D010342:Patient Acceptance of Health Care

Discrimination
Health service use
Intersectional approaches
Community health
Epidemiology
Population survey


Sequence Similarities between Viroids and Human MicroRNAs.

Abstract: Viroids are minute unencapsidated non-coding circular RNAs known to be present and to cause diseases only in plants. Infections were associated with the occurrence of specific single-stranded RNAs similar in size to miRNAs and endogenous small interfering RNAs, and viroid pathogenicity is suspected to occur through RNA interference. We looked for sequence similarities between viroids and the seed region of human microRNAs (hsa-miRNAs). Viroid genomes were retrieved from GenBank and mature hsa-mi-RNAs were retrieved from miRBase. Two hundred 300-nucleotide-long sequences were randomly generated as controls. BLAST searches were performed using viroids as queries and hsa-miRNAs as subjects with relaxed parameters, and matches involving hsa-miRNA seed regions were considered. A total of 81,021 matches were found, and 1,501 that showed 100% identity with whole hsa-miRNA seed regions were selected. The most frequent matches involved Chrysanthemum stunt viroid or Hop stunt viroidspecies with hsa-miR-4286, in 365 and 207 cases, respectively. Three hsa-mi-RNAs (miR-4286, miR-6808-5p, and miR-3622a-3p) were involved in 47% of all matches between viroids and hsa-mi-RNAs. Taken together, these findings warrant further investigation on the potential of viroids and their derived small RNAs to cross kingdoms and interact with nucleic acids in humans.

Bengone-Abogourin|Jessica Grace|JG|
Chelkha|Nisrine|N|
Verdin|Eric|E|
Colson|Philippe|P|

Viroid
Human
microRNA
Plants
RNA interference
Messenger RNA


Individual-level socioeconomic status and community-level inequality as determinants of stigma towards persons living with HIV who inject drugs in Thai Nguyen, Vietnam.

Abstract:
INTRODUCTION
HIV infection may be affected by multiple complex socioeconomic status (SES) factors, especially individual socioeconomic disadvantage and community-level inequality. At the same time, stigma towards HIV and marginalized groups has exacerbated persistent concentrated epidemics among key populations, such as persons who inject drugs (PWID) in Vietnam. Stigma researchers argue that stigma fundamentally depends on the existence of economic power differences in a community. In rapidly growing economies like Vietnam, the increasing gap in income and education levels, as well as an individual's absolute income and education, may create social conditions that facilitate stigma related to injecting drug use and HIV.

METHODS
A cross-sectional baseline survey assessing different types of stigma and key socioeconomic characteristics was administered to 1674 PWID and 1349 community members living in physical proximity throughout the 32 communes in Thai Nguyen province, Vietnam. We created four stigma scales, including HIV-related and drug-related stigma reported by both PWID and community members. We then used ecologic Spearman's correlation, ordinary least-squares regression and multi-level generalized estimating equations to examine community-level inequality associations, individual-level SES associations and multi-level SES associations with different types of stigma, respectively.

RESULTS
There was little urban-rural difference in stigma among communes. Higher income inequality was marginally associated with drug-related stigma reported by community members (p=0.087), and higher education inequality was significantly associated with higher HIV-related stigma reported by both PWID and community members (p<0.05). For individuals, higher education was significantly associated with lower stigma (HIV and drug related) reported by both PWID and community members. Part-time employed PWID reported more experiences and perceptions of drug-related stigma, while conversely unemployed community members reported enacting lower drug-related stigma. Multi-level analysis revealed that the relationship between education inequality and HIV-related stigma is superseded by the effect of individual-level education.

CONCLUSIONS
The results of the study confirm that socioeconomic factors at both the individual level and community level affect different types of stigma in different ways. Attention should be paid to these differences when planning structural or educational interventions to reduce stigma, and additional research should investigate the mechanisms with which SES and inequality affect social relationships and, in turn, stigma.

Lim|Travis|T|
Zelaya|Carla|C|
Latkin|Carl|C|
Quan|Vu Minh|VM|
Frangakis|Constantine|C|
Ha|Tran Viet|TV|
Minh|Nguyen Le|NL|
Go|Vivian|V|

D003430:Cross-Sectional Studies
D004192:Discrimination, Psychological
D015658:HIV Infections
D006801:Humans
D012923:Social Class
D057545:Social Stigma
D012959:Socioeconomic Factors
D015819:Substance Abuse, Intravenous
D014744:Vietnam

socioeconomic status
stigma
HIV
persons who inject drugs
income inequality
GINI coefficient
injection drug users
multi-level model
social determinants of health


Effects of dietary white mulberry leaves on hemato-biochemical alterations, immunosuppression and oxidative stress induced by Aeromonas hydrophila in Oreochromis niloticus.

Abstract: The present work was designed to assess the potential hemato-biochemical protective action, immunemodulatory and antioxidant conclusions of varied concentration of white mulberry Morus alba leaves (MAL) extract supplementation on Nile tilapia (Oreochromis .niloticus). A total two hundred and forty of O. niloticus were haphazardly sorted into four groups. The control (CT) group was fed on basal diet. A group MAL1, MAL3 and MAL5 was fed on 1, 3 and 5 g/kg MAL respectively for thirty days. On day thirty one, half of replicates in each group were challenged by 0.5 ml × 108Aeromonas hydrophila where, the residual replicates were kept without challenge. A. hydrophila challenged tilapias revealed anemia that alleviated by supplementation with 5 g/kg MAL also, recovers the shift of leucogram prompted by the challenge. Elevation of alkaline phosphatase, aminotransferases, lactate dehydrogenase and malondialdehyde (ALP, ALT, AST, LDH and MDA) in CT, MAL1 and MAL3 in the challenged replicates respectively where within normal at MAL5. Supplementation with MAL5 showed more potent antioxidant and immune reaction than MAL1 and MAL3. There were a rapid increase of immunoglobulin M, lysozymes, nitric oxide, catalase and superoxide dismutase and their allied genes expression (IgM, CAT and SOD) in MAL groups with contrast in CT challenged groups. Where in challenged groups, there was suppression in genes expression of interleukins (8 and 1 beta) and interferon ɤ (IL8. IL-1β and INFɤ). Tilapias challenged by A. hydrophila unveiled plentiful surge in the percentage of mortality in CT challenged fish (80%), followed by the groups supplemented with MAL1 and MAL3 were (73.33%) where MAL5 was 20%. The mortalities have been halted from the 6th, 13th, 14th and 15th days in, MAL5, MAL3, MAL1, and CT correspondingly. These previous results could be fulfilled that using of MAL 5 g/kg protect tilapias from hemato-biochemical alterations and enhance its immune feedback, antioxidant defense and resistance against A. hydrophila.

Neamat-Allah|Ahmed N F|ANF|
Mahmoud|Essam A|EA|
Mahsoub|Y|Y|

Mulberry
Morus alba
MAL
Nile tilapia
Cytokines
Hematology
Hydrophila spp
Immune response


The role of IRAS/Nischarin involved in the development of morphine tolerance and physical dependence.

Abstract: Morphine is a potent opioid analgesic used to alleviate moderate or severe pain, but the development of drug tolerance and dependence limits its use in pain management. Our previous studies showed that the candidate protein for I1 imidazoline receptor, imidazoline receptor antisera-selected (IRAS)/Nischarin, interacts with μ opioid receptor (MOR) and modulates its trafficking. However, there is no report of the effect of IRAS on morphine tolerance and physical dependence. In the present study, we found that IRAS knockout (KO) mice showed exacerbated analgesic tolerance and physical dependence compared to wild-type (WT) mice by chronic morphine treatment. Chronic morphine treatment down-regulated the expression of MOR in spinal cord of IRAS KO mice, while had no significant effect on MOR expression in WT mice. We observed the compensatory increase of cAMP accumulation in spinal cord after morphine tolerance, and this change was more significant in KO mice than WT mice. Furthermore, KO mice showed more elevation in the phosphorylation of AMPA receptor GluR1-S845 than WT mice, while the total expression of GluR1 remained unchanged after morphine dependence. Altogether, these data suggest that IRAS may play an important role in the development of morphine tolerance and physical dependence in vivo through modulating MOR expression, as well as AMPA GluR1-S845 phosphorylation, which might be one of the mechanisms underlying the development of opiate addiction.

Li|Shuo|S| Wu|Ning|N| Zhao|Tai-Yun|TY| Lu|Guan-Yi|GY| Wang|Zhi-Yuan|ZY| Li|Fei|F| Li|Jin|J|

D000701:Analgesics, Opioid
D000818:Animals
D000242:Cyclic AMP
D004361:Drug Tolerance
D054755:Imidazoline Receptors
D051379:Mice
D018345:Mice, Knockout
D009020:Morphine
D009021:Morphine Dependence

IRAS Morphine Tolerance Dependence GluR1-S845


Assessment of Pulmonary Edema: Principles and Practice.

Abstract: Pulmonary edema increasingly is recognized as a perioperative complication affecting outcome. Several risk factors have been identified, including those of cardiogenic origin, such as heart failure or excessive fluid administration, and those related to increased pulmonary capillary permeability secondary to inflammatory mediators. Effective treatment requires prompt diagnosis and early intervention. Consequently, over the past 2 centuries a concentrated effort to develop clinical tools to rapidly diagnose pulmonary edema and track response to treatment has occurred. The ideal properties of such a tool would include high sensitivity and specificity, easy availability, and the ability to diagnose early accumulation of lung water before the development of the full clinical presentation. In addition, clinicians highly value the ability to precisely quantify extravascular lung water accumulation and differentiate hydrostatic from high permeability etiologies of pulmonary edema. In this review, advances in understanding the physiology of extravascular lung water accumulation in health and in disease and the various mechanisms that protect against the development of pulmonary edema under physiologic conditions are discussed. In addition, the various bedside modalities available to diagnose early accumulation of extravascular lung water and pulmonary edema, including chest auscultation, chest roentgenography, lung ultrasonography, and transpulmonary thermodilution, are examined. Furthermore, advantages and limitations of these methods for the operating room and intensive care unit that are critical for proper modality selection in each individual case are explored.

Assaad|Sherif|S|
Kratzert|Wolf B|WB|
Shelley|Benjamin|B|
Friedman|Malcolm B|MB|
Perrino|Albert|A|

pulmonary edema
auscultation
transpulmonary thermodilution
chest radiography
lung ultrasound


Appointed by young people - a qualitative study on young patients recruiting hospital staff in Denmark.

Abstract:
BACKGROUND
There is a lack of knowledge about young peoples'wishes for the qualifications including skills and personal traits of hospital staff during the recruitment process.

OBJECTIVE
The aim of this qualitative study was to explore which qualifications, skills and personal traits young people prefer when recruiting hospital staff.

METHODS
A Youth Recruitment Committee (YRC) consisting of four young people performed six job interviews in parallel to conventional job interviews at Copenhagen University Hospital Rigshospitalet, Denmark. The interviews with the candidates and the subsequent YRC deliberation were observed and recorded, and data were analyzed using thematic analysis.

RESULTS
Four main themes with matching sub-themes emerged from the data: (1) Personality (appearance and commitment), (2) Professional skills (approach, mentality and activities), (3) Project management (skills and experience), (4) Communication (during the interview and experiential approach to youth). It was important to the YRC that the candidate had professional experience working with young people as well as being a skilled project manager. The YRC also assessed the candidates´ communication during the interview.

CONCLUSIONS
By inviting young people in as a separate recruitment committee, their perspectives and preferences were noted without interference from professionals. Our findings are in line with previous research regarding young peoples´ preferences on youth-friendly health services. Furthermore, this approach made it possible to evaluate candidates´ communication skills with young people as they were assessed during the job interviews.

Hanghøj|Signe|S|
Thomsen|Ena L|EL|
Blix|Charlotte|C|
Hertz|Pernille Grarup|PG|
Boisen|Kirsten A|KA|

qualitative
recruitment
hospital staff
qualifications
communication
adolescents
participation
user involvement


Successful use of ultrasound-guided caudal catheter in a child with a very low termination of dural sac and Opitz-GBBB syndrome: a case report.

Abstract: We report a 2-year-old patient with Opitz-GBBB syndrome scheduled for a posterior sagittal anorectoplasty (PSARP). The ultrasound scan revealed the inferior end of dural sac just below sacrococcygeal membrane, although the patient had previously two successful caudal epidural blocks. Consequently, the epidural catheter was inserted under a real-time ultrasound guidance without dural puncture. Our patient had excellent pain relief without any side effects.

caudal
child
Opitz-GBBB syndrome
ultrasound
pain
anesthesia
spinal canal


Knowledge, Attitude, and Practice of Physicians Regarding Vaccinations in Yerevan, Armenia: A Case Study of HPV.

Abstract: This paper highlights the low levels of vaccine coverage and high levels of reported vaccination hesitancy in Yerevan, Armenia, that present profound challenges to the control of disease through routine vaccination programmes. We draw on investigations of hesitancy towards the introduction of new vaccines, using the Human Papillomavirus (HPV) vaccine Gardasil as a case study, to interrogate underlying challenges to vaccine acceptance. We analyse primary data from the introduction of Gardasil, first used in Armenia in 2017, to investigate how levels of medical knowledge amongst physicians in 20 health facilities in Yerevan, Armenia, regarding vaccine science influence attitudes towards the introduction of a newly developed vaccine. A questionnaire-based cross-sectional study was completed by 348 physicians between December 2017 and September 2018. The responding physicians displayed a respectable level of knowledge and awareness regarding vaccination with respect to some characteristics (e.g., more than 81% knew that HPV infection was commonly asymptomatic, 73% knew that HPV infection was implicated in most cervical cancers, and 87% knew that cervical cancer is the most prevalent cancer amongst women) but low knowledge and poor understanding of other key issues such as the age at which women were most likely to develop cervical cancer (only 15% answered correctly), whether or not the vaccine should be administered to people who had already been infected (27% answered correctly) and whether sexually active young people should be treated for infection before vaccination (26% answered correctly). The study suggests that the drivers of vaccine hesitancy are complex and may not be consistent from vaccine to vaccine. The Armenian healthcare sector may need to provide additional training, awareness-raising and educational activities alongside the introduction of new vaccines to improve understanding of and trust in vaccination programmes.

Badalyan|Arman R|AR|
Hovhannisyan|Marine|M|
Ghavalyan|Gayane|G|
Ter-Stepanyan|Mary M|MM|
Cave|Rory|R|
Cole|Jennifer|J|0000-0001-8787-8892
Farlow|Andrew W K|AWK|
Mkrtchyan|Hermine V|HV|

HPV
vaccine hesitancy
Gardasil
cervical cancer
immunization
vaccine confidence